UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 6-K
REPORT OF FOREIGN PRIVATE ISSUER
PURSUANT TO RULE 13a-16 OR 15d-16
UNDER THE SECURITIES EXCHANGE ACT OF 1934
For the month of June 2021
Commission File Number: 001-40212
Connect Biopharma Holdings Limited
(Translation of registrant’s name into English)
Science and Technology Park
East R&D Building, 3rd Floor
6 Beijing West Road, Taicang
Jiangsu Province, China 215400
(Address of principal executive office)
Indicate by check mark whether the registrant files or will file annual reports under cover of Form 20-F or Form 40-F.
Form 20-F ☒ Form 40-F ☐
Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(1): ☐
Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(7): ☐
On May 25, 2021, Connect Biopharma Holdings Limited (the “Company”) issued the press release attached hereto as Exhibit 99.1, which is incorporated herein by reference.
On June 2, 2021, spokespersons of the Company presented the information in the presentation slides attached hereto as Exhibit 99.2 in a previously announced webcast. The Company posted the updated corporate presentation to the Company’s website, www.connectbiopharm.com. The Company plans to use its website to disseminate future updates to its corporate presentation and does not intend to furnish a Form 6-K alerting investors each time the presentation is updated.
The furnishing of the attached presentation is not an admission as to the materiality of any information therein. The information contained in the presentation is summary information that is intended to be considered in the context of more complete information included in the Company’s filings with the Securities and Exchange Commission (the “SEC”) and other public announcements that the Company has made and may make from time to time. The Company undertakes no duty or obligation to update or revise the information contained in this report, although it may do so from time to time as its management believes is appropriate. Any such updating may be made through the filing or furnishing of other reports or documents with the SEC or through other public disclosures.
Exhibit Index
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.
| Dated: June 3, 2021 | CONNECT BIOPHARMA HOLDINGS LIMITED | |||||
| By | /s/ Eric Hall | |||||
| Name: | Eric Hall | |||||
| Title: | Interim Chief Financial Officer | |||||
Exhibit 99.1
Connect Biopharma Announces First Subject Dosed in Phase I Trial Evaluating Safety, Tolerability and Pharmacokinetic Profile of CBP-174 in Healthy Adult Subjects
Development program exploring the potential of CBP-174 in the treatment of chronic inflammatory pruritus
SAN DIEGO and TAICANG, SUZHOU, China, May 25, 2021 (GLOBE NEWSWIRE) — Connect Biopharma Holdings Limited (Nasdaq: CNTB) (“Connect Biopharma” or the “Company”), a global clinical-stage biopharmaceutical company dedicated to improving the lives of patients with chronic inflammatory diseases through the development of therapies derived from T cell-driven research, today announced that the first subject has been dosed in a Phase I trial evaluating CBP-174 in healthy adult subjects.
This randomized, double-blind, placebo-controlled, single ascending dose trial in healthy subjects, aims to evaluate the safety, tolerability and pharmacokinetics of CBP-174 in different dose levels given orally, compared to placebo. Following the single dose, each subject will be followed for up to seven days (NCT04811469).
“The effective management of pruritus associated with atopic dermatitis and other inflammatory skin conditions remains a significant unmet medical need, and the advancement of this novel oral agent into Phase I trial is an important step forward in the development of potential therapies,” said Zheng Wei, PhD, Co-founder and CEO of Connect Biopharma. “We believe that CBP-174’s novel mechanism of action and rapid onset of action has the potential to complement the anti-pruritic effect of disease-modifying agents already approved for inflammatory skin diseases.”
About Chronic Inflammatory Pruritus
Chronic inflammatory pruritus is an unpleasant and often persistent itch that can last more than six weeks in duration and is often caused by inflamed skin lesions associated with diseases such as atopic dermatitis (AD). Due to the significant impact that pruritus has on quality of life, its severity is often measured by patients based on intensity of pruritus rather than skin lesions themselves. Common antihistamine drugs primarily target the histamine 1 receptor (H1R) and lead to alleviation of itch in part by blocking H1R on peripheral nerves. However, many types of chronic itch cannot be relieved by current antihistamine treatments that target H1R. Despite currently available treatments for AD, an estimated 40% to 50% of AD patients have inadequate relief of their pruritus and are in need of new, efficacious pruritus therapies.
About CBP-174
CBP-174 is a highly potent, orally active, peripherally restricted antagonist of histamine receptor 3 (H3R), designed not to penetrate the blood brain barrier. In preclinical studies, CBP-174 was both well-tolerated and demonstrated significant reductions in scratching bouts within the first 30 minutes of oral or topical dosing, which could potentially translate to rapid relief of itch in the clinic.
About Connect Biopharma Holdings Limited
Connect Biopharma Holdings Limited is a global clinical-stage biopharmaceutical company dedicated to improving the lives of patients living with chronic inflammatory diseases through the development of therapies derived from our T cell-driven research.
Our lead product candidate, CBP-201, is an antibody designed to target interleukin-4 receptor alpha (IL-4Rα) and is currently being evaluated in clinical trials for the treatment of atopic dermatitis (AD) and asthma and in development for chronic rhinosinusitis with nasal polyps (CRSwNP). Our second lead product candidate is CBP-307, a modulator of a T cell receptor known as sphingosine 1-phosphate receptor 1 (S1P1) that is in development for the treatment of ulcerative colitis (UC) and Crohn’s disease (CD). Furthermore, we are developing CBP-174, a peripherally restricted antagonist of histamine receptor 3, for the treatment of pruritus associated with skin inflammation.
With headquarters in China, additional operations in the United States and Australia, and clinical development activities in those geographies as well as Europe, Connect Biopharma is building a rich global pipeline of internally designed, wholly owned small molecules and antibodies targeting several aspects of T cell biology. For additional information about Connect Biopharma, please visit our website at www.connectbiopharm.com.
FORWARD-LOOKING STATEMENTS
Connect Biopharma cautions that statements included in this press release that are not a description of historical facts are forward-looking statements. Words such as “may,” “could,” “will,” “would,” “should,” “expect,” “plan,” “anticipate,” “believe,” “estimate,” “intend,” “predict,” “seek,” “contemplate,” “potential,” “continue” or “project” or the negative of these terms or other comparable terminology are intended to identify forward-looking statements. These statements include the Company’s statements regarding the potential of CBP-174 to address the unmet needs of patients with chronic inflammatory pruritus. The inclusion of forward-looking statements should not be regarded as a representation by Connect Biopharma that any of its plans will be achieved. Actual results may differ from those set forth in this release due to the risks and uncertainties inherent in the Connect Biopharma business and other risks described in the Company’s filings with the Securities and Exchange Commission (“SEC”). Investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and Connect Biopharma undertakes no obligation to revise or update this news release to reflect events or circumstances after the date hereof. Further information regarding these and other risks is included in Connect Biopharma’s filings with the SEC which are available from the SEC’s website (www.sec.gov) and on Connect Biopharma’s website (www.connectbiopharm.com) under the heading “Investors.” All forward-looking statements are qualified in their entirety by this cautionary statement. This caution is made under the safe harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995.
IR/PR Contacts:
Lazar FINN Partners
David Carey (IR)
T: +1-(212) 867-1768
david.carey@finnpartners.com
Erich Sandoval (Media)
T: +1-(917)-497-2867
erich.sandoval@finnpartners.com
Corporate Contacts:
info@connectpharm.com
Exhibit 99.2 DEVELOPING NEXT-GENERATION THERAPEUTICS FOR T CELL DRIVEN INFLAMMATORY DISEASES Corporate Presentation - June 2021 NASDAQ: CNTBExhibit 99.2 DEVELOPING NEXT-GENERATION THERAPEUTICS FOR T CELL DRIVEN INFLAMMATORY DISEASES Corporate Presentation - June 2021 NASDAQ: CNTB
2 Forward-Looking Statements • Certain information contained in this presentation relates to, or is based on, studies, publications, surveys and other data obtained from third-party sources and Connect’s own internal estimates and research. While we believe these third-party sources to be reliable as of the date of this presentation, we have not independently verified, and make no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. In addition, all of the market data included in this presentation involves a number of assumptions and limitations, and there can be no guarantee as to the accuracy or reliability of such assumptions. Finally, while we believe our own internal research is reliable, such research has not been verified by any independent source. • This presentation contains forward-looking statements that involve substantial risks and uncertainties. All statements other than statements of historical facts contained in this presentation, including statements regarding our future financial condition, results of operations, business strategy and plans, prospective products, product approvals, research and development plans and costs, timing and likelihood of success, objectives of management for future operations and future results of anticipated product development efforts, as well as statements regarding industry trends, are forward-looking statements. Forward-looking statements can be identified by words such as: “anticipate,” “believe,” “contemplate,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” or “would” or the negative of these terms or other similar expressions. The forward-looking statements in this presentation are only predictions. We have based these forward-looking statements largely on our current expectations and projections about future events and trends that we believe may affect our financial condition, results of operations, business strategy and financial needs. These forward-looking statements are inherently subject to a number of risks, uncertainties and assumptions, some of which cannot be predicted or quantified and some of which are beyond our control, including, among other things: the ability of our clinical trials to demonstrate safety and efficacy of our product candidates, and other positive results; our ability to obtain and maintain regulatory approval of our product candidates; existing regulations and regulatory developments in the United States, the PRC, Europe and other jurisdictions; uncertainties regarding the interpretation and enforcement of PRC laws, rules and regulations; risks associated with the COVID-19 outbreak, which has and may continue to materially and adversely impact our business, preclinical studies and clinical trials; our plans and ability to obtain, maintain, protect and enforce our intellectual property rights and our proprietary technologies, including extensions of existing patent terms where available; our continued reliance on third parties to conduct additional clinical trials of our product candidates, and for the manufacture of our product candidates for preclinical studies and clinical trials; and the degree of market acceptance of our product candidates by physicians, patients, healthcare payors and others in the medical community. These risks are not exhaustive. • New risk factors emerge from time to time and it is not possible for our management to predict all risk factors, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in, or implied by, any forward-looking statements. You should not rely upon forward-looking statements as predictions of future events. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance or achievements. Except as required by law, we undertake no obligation to update publicly any forward-looking statements for any reason after the date of this presentation. • In addition, statements that “we believe” and similar statements reflect our beliefs and opinions on the relevant subject. These statements are based upon information available to us as of the date of this presentation, and while we believe such information forms a reasonable basis for such statements, such information may be limited or incomplete, and our statements should not be read to indicate that we have conducted an exhaustive inquiry into, or review of, all potentially available relevant information. These statements are inherently uncertain and investors are cautioned not to unduly rely upon these statements.2 Forward-Looking Statements • Certain information contained in this presentation relates to, or is based on, studies, publications, surveys and other data obtained from third-party sources and Connect’s own internal estimates and research. While we believe these third-party sources to be reliable as of the date of this presentation, we have not independently verified, and make no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. In addition, all of the market data included in this presentation involves a number of assumptions and limitations, and there can be no guarantee as to the accuracy or reliability of such assumptions. Finally, while we believe our own internal research is reliable, such research has not been verified by any independent source. • This presentation contains forward-looking statements that involve substantial risks and uncertainties. All statements other than statements of historical facts contained in this presentation, including statements regarding our future financial condition, results of operations, business strategy and plans, prospective products, product approvals, research and development plans and costs, timing and likelihood of success, objectives of management for future operations and future results of anticipated product development efforts, as well as statements regarding industry trends, are forward-looking statements. Forward-looking statements can be identified by words such as: “anticipate,” “believe,” “contemplate,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” or “would” or the negative of these terms or other similar expressions. The forward-looking statements in this presentation are only predictions. We have based these forward-looking statements largely on our current expectations and projections about future events and trends that we believe may affect our financial condition, results of operations, business strategy and financial needs. These forward-looking statements are inherently subject to a number of risks, uncertainties and assumptions, some of which cannot be predicted or quantified and some of which are beyond our control, including, among other things: the ability of our clinical trials to demonstrate safety and efficacy of our product candidates, and other positive results; our ability to obtain and maintain regulatory approval of our product candidates; existing regulations and regulatory developments in the United States, the PRC, Europe and other jurisdictions; uncertainties regarding the interpretation and enforcement of PRC laws, rules and regulations; risks associated with the COVID-19 outbreak, which has and may continue to materially and adversely impact our business, preclinical studies and clinical trials; our plans and ability to obtain, maintain, protect and enforce our intellectual property rights and our proprietary technologies, including extensions of existing patent terms where available; our continued reliance on third parties to conduct additional clinical trials of our product candidates, and for the manufacture of our product candidates for preclinical studies and clinical trials; and the degree of market acceptance of our product candidates by physicians, patients, healthcare payors and others in the medical community. These risks are not exhaustive. • New risk factors emerge from time to time and it is not possible for our management to predict all risk factors, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in, or implied by, any forward-looking statements. You should not rely upon forward-looking statements as predictions of future events. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance or achievements. Except as required by law, we undertake no obligation to update publicly any forward-looking statements for any reason after the date of this presentation. • In addition, statements that “we believe” and similar statements reflect our beliefs and opinions on the relevant subject. These statements are based upon information available to us as of the date of this presentation, and while we believe such information forms a reasonable basis for such statements, such information may be limited or incomplete, and our statements should not be read to indicate that we have conducted an exhaustive inquiry into, or review of, all potentially available relevant information. These statements are inherently uncertain and investors are cautioned not to unduly rely upon these statements.
3 Connect is Well-Positioned for Value Creation Targeting inflammatory diseases (Dermatology, Gastroenterology, Respiratory) with high unmet need Large Opportunity Ambition to develop molecules with “First-in-class” or “Best-in-class” potential CBP-201:- Interleukin-4-receptor alpha (IL4Ra) blocker Clinical Stage with Deep CBP-307:- Sphingosine 1-phosphate-1 (S1P1) Pipeline CBP-174:- Peripherally acting Histamine-3 Receptor (H3R) antagonist Prolific Validated, T cell-modulating discovery designed to enhance and speed up the identification of Discovery Engine potentially highly differentiated immune modulators Seasoned industry leaders with significant experience in immunology drug discovery and Global Outlook development; building an internal and external team to drive Greater China and USA development Strong Investor ~$440 million raised to date from top-tier investors, with IPO in March 2021 raising ~$220M (NASDAQ: CNTB) and a Series C ($135M) completed in December 2020 Support Multiple Anticipated 3x clinical trial data read outs by end Q1 2022, and a total 6x clinical trial data read outs by catalysts end Q1 2023, across 4x diseases 3 Connect is Well-Positioned for Value Creation Targeting inflammatory diseases (Dermatology, Gastroenterology, Respiratory) with high unmet need Large Opportunity Ambition to develop molecules with “First-in-class” or “Best-in-class” potential CBP-201:- Interleukin-4-receptor alpha (IL4Ra) blocker Clinical Stage with Deep CBP-307:- Sphingosine 1-phosphate-1 (S1P1) Pipeline CBP-174:- Peripherally acting Histamine-3 Receptor (H3R) antagonist Prolific Validated, T cell-modulating discovery designed to enhance and speed up the identification of Discovery Engine potentially highly differentiated immune modulators Seasoned industry leaders with significant experience in immunology drug discovery and Global Outlook development; building an internal and external team to drive Greater China and USA development Strong Investor ~$440 million raised to date from top-tier investors, with IPO in March 2021 raising ~$220M (NASDAQ: CNTB) and a Series C ($135M) completed in December 2020 Support Multiple Anticipated 3x clinical trial data read outs by end Q1 2022, and a total 6x clinical trial data read outs by catalysts end Q1 2023, across 4x diseases
Connect’s discovery approach is designed to offer significant 4 speed and mechanistic advantages … T Cell SCREENING LIBRARY Affinity Signaling Modulation Drug Candidate Traditional Method Requires more steps, yields fewer candidates and may miss molecules with potent T cell modulation activity Candidates may be rejected early due to low binding affinity even though they are functionally very T Cell Modulation potent (false negative) Drug Candidate Method Rapidly identifies all molecules with potent T cell modulation activityConnect’s discovery approach is designed to offer significant 4 speed and mechanistic advantages … T Cell SCREENING LIBRARY Affinity Signaling Modulation Drug Candidate Traditional Method Requires more steps, yields fewer candidates and may miss molecules with potent T cell modulation activity Candidates may be rejected early due to low binding affinity even though they are functionally very T Cell Modulation potent (false negative) Drug Candidate Method Rapidly identifies all molecules with potent T cell modulation activity
5 A pipeline of potentially highly differentiated therapies Connect Biopharma has Global Development & Commercialization Rights to all Product Candidates INDICATION PRECLINICAL PHASE 1 PHASE 2 PHASE 3 Atopic Dermatitis (AD) CBP-201 Antibody targeting IL-4Rα Asthma cytokine receptor (Th2 cell modulator) Chronic Rhinosinusitis with Nasal * Polyps (CRSwNP) Ulcerative Colitis (UC) CBP-307 Small molecule targeting ^ S1P1 (Th1 cell modulator) Crohn’s Disease (CD) CBP-174 Pruritus associated with AD Peripherally restricted H3 receptor antagonist CBP-233 Allergic Inflammation Antibody targeting IL-33 * Advancing into Phase 2. We plan to initiate a Phase 2 Clinical Trial in CRSwNP, based on PK results from our completed Phase 1a study in healthy volunteers ^ Phase 2 Study ended early due to COVID-19-related enrolment challenges. New trial planned 5 A pipeline of potentially highly differentiated therapies Connect Biopharma has Global Development & Commercialization Rights to all Product Candidates INDICATION PRECLINICAL PHASE 1 PHASE 2 PHASE 3 Atopic Dermatitis (AD) CBP-201 Antibody targeting IL-4Rα Asthma cytokine receptor (Th2 cell modulator) Chronic Rhinosinusitis with Nasal * Polyps (CRSwNP) Ulcerative Colitis (UC) CBP-307 Small molecule targeting ^ S1P1 (Th1 cell modulator) Crohn’s Disease (CD) CBP-174 Pruritus associated with AD Peripherally restricted H3 receptor antagonist CBP-233 Allergic Inflammation Antibody targeting IL-33 * Advancing into Phase 2. We plan to initiate a Phase 2 Clinical Trial in CRSwNP, based on PK results from our completed Phase 1a study in healthy volunteers ^ Phase 2 Study ended early due to COVID-19-related enrolment challenges. New trial planned
Multiple Clinical Trial Catalysts Anticipated In Next 24 Months 6 (Subject to ongoing Covid-19 restrictions) CBP-201 CBP-201 CBP-201 AD Ph2 AD Ph2b AD Ph3 Full Enrollment Topline Launch CBP-201 CBP-201 CBP-201 Asthma Asthma Ph2 Asthma Ph2 Ph2 Launch Full Enrollment Topline CBP-201 CBP-201 CBP-201 CRSwNP CRSwNP Ph2 CRSwNP Ph2 Ph2 Full Enrollment Launch Topline CBP-174 CBP-174 CBP-174 CBP-174 CBP-174 Ph1a Ph1a Ph1b Ph1b Ph1b Launch Topline Launch Full Enrollment Topline CBP-307 CBP-307 CBP-307 UC Ph2 UC Ph2 UC Ph3 Full Enrollment Topline Launch CBP-201 CBP-201 AD China Ph2/3 AD China Ph2/3 Launch Full Enrollment Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 2021 2022 2023 ^ A CBP-307 CD trial is currently planned Multiple Clinical Trial Catalysts Anticipated In Next 24 Months 6 (Subject to ongoing Covid-19 restrictions) CBP-201 CBP-201 CBP-201 AD Ph2 AD Ph2b AD Ph3 Full Enrollment Topline Launch CBP-201 CBP-201 CBP-201 Asthma Asthma Ph2 Asthma Ph2 Ph2 Launch Full Enrollment Topline CBP-201 CBP-201 CBP-201 CRSwNP CRSwNP Ph2 CRSwNP Ph2 Ph2 Full Enrollment Launch Topline CBP-174 CBP-174 CBP-174 CBP-174 CBP-174 Ph1a Ph1a Ph1b Ph1b Ph1b Launch Topline Launch Full Enrollment Topline CBP-307 CBP-307 CBP-307 UC Ph2 UC Ph2 UC Ph3 Full Enrollment Topline Launch CBP-201 CBP-201 AD China Ph2/3 AD China Ph2/3 Launch Full Enrollment Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 2021 2022 2023 ^ A CBP-307 CD trial is currently planned
7 Leading Global Investors, Strong Cash Position Funded through end of 2022 • $220 million raised pre-IPO ‒ Completed $135 million Series C led by RA Capital in December 2020 • ~$220 million raised at IPO, closed March 2021 (NASDAQ: CNTB) ‒ Underwriters’ option to purchase exercised in full ‒ Jefferies LLC, SVB Leerink LLC, Piper Sandler & Co. and China International Capital Corporation Hong Kong Securities Limited acted as joint book-running managers for the offering ‒ Oversubscribed with strong institutional support from Fidelity, Wellington, Cormorant, Janus, and over 75 other institutional investors7 Leading Global Investors, Strong Cash Position Funded through end of 2022 • $220 million raised pre-IPO ‒ Completed $135 million Series C led by RA Capital in December 2020 • ~$220 million raised at IPO, closed March 2021 (NASDAQ: CNTB) ‒ Underwriters’ option to purchase exercised in full ‒ Jefferies LLC, SVB Leerink LLC, Piper Sandler & Co. and China International Capital Corporation Hong Kong Securities Limited acted as joint book-running managers for the offering ‒ Oversubscribed with strong institutional support from Fidelity, Wellington, Cormorant, Janus, and over 75 other institutional investors
CBP-201: A next generation anti-interleukin-4-receptor alpha (IL-4Rα) antibody in development for type 2 inflammatory diseasesCBP-201: A next generation anti-interleukin-4-receptor alpha (IL-4Rα) antibody in development for type 2 inflammatory diseases
9 CBP-201: A Next Generation IL-4Rα Blocker Mechanism of Action - Dual Inhibition of IL-4 and IL-13 – A validated target IL-4/IL-13 Pathway Dual Inhibition is Effective Across Many Th2-mediated diseases • CBP-201 is a novel, human monoclonal IgG4 antibody directed against IL-4Rα, a common subunit for IL-4 and IL- 13 receptors • Blockade of IL-4 and IL-13 binding to IL4Rα results in inhibition of both IL-4 and IL-13 signaling • Potential for differentiation based on observations of 1. Different IL-4Rα binding epitope to dupilumab • Higher binding affinity and potency for IL-4Rα 2. CBP-201 detected longer in plasma than dupilumab • Slower receptor mediated clearance • Potential for clinical results to show ‒ Faster onset of action ‒ Greater clinical response ‒ Less frequent dosing (Q4W)9 CBP-201: A Next Generation IL-4Rα Blocker Mechanism of Action - Dual Inhibition of IL-4 and IL-13 – A validated target IL-4/IL-13 Pathway Dual Inhibition is Effective Across Many Th2-mediated diseases • CBP-201 is a novel, human monoclonal IgG4 antibody directed against IL-4Rα, a common subunit for IL-4 and IL- 13 receptors • Blockade of IL-4 and IL-13 binding to IL4Rα results in inhibition of both IL-4 and IL-13 signaling • Potential for differentiation based on observations of 1. Different IL-4Rα binding epitope to dupilumab • Higher binding affinity and potency for IL-4Rα 2. CBP-201 detected longer in plasma than dupilumab • Slower receptor mediated clearance • Potential for clinical results to show ‒ Faster onset of action ‒ Greater clinical response ‒ Less frequent dosing (Q4W)
10 CBP-201: Phase 1b – Trial Design & Primary Endpoint AE Profile Consistent with Data Reported in Studies of Existing IL-4Ra Blockers A Randomized, Double-Blind, Placebo-Controlled Multi-Centered, Dose-Escalation Trial of Safety, Pharmacokinetics and Pharmacodynamics of CBP-201 in Adult Subjects With Moderate-to-Severe Atopic Dermatitis Study conducted in 13 centers in Australia and New Zealand 4 Weeks 7 Weeks 75 mg/Placebo (4:1), Safety n=10 Follow-up • No serious adverse events (SAEs) and no injection site Screening Cohort 1 4 Weeks 7 Weeks reaction or conjunctivitis / keratitis AEs Randomization 150 mg/Placebo (4:1). Safety Baseline n=10 Follow-up • No dose proportional effect on TEAEs either by frequency Screening Cohort 2 4 Weeks 7 Weeks Randomization or severity 300 mg/Placebo (4:1), Safety Baseline n=10 Follow-up Screening • Most TEAEs were mild in severity, with the majority Cohort 3 Randomization deemed unrelated to CBP-201 Baseline • A single TEAE (atopic dermatitis flare) leading to study Primary Endpoint: (At week 11) treatment discontinuation in one subject in each of the • Safety and tolerability CBP-201 75mg and placebo groups Exploratory Efficacy Endpoints: (At week 4) • Percent change in EASI from Baseline • Proportion of patients achieving IGA of 0 or 1 (clear or almost clear) (IGA 0,1) • Change in total affected BSA from baseline BSA: Body Surface Area EASI: Eczema Area and Severity Index IGA: Investigator’s Global Assessment P-NRS: Pruritus Numeric Rating Scale • Change in P-NRS from baseline (pruritus intensity and frequency) DLQI: Dermatology Life Quality Index • A randomized, double-blind, placebo-controlled, multiple ascending dose study of the safety, pharmacokinetics and preliminary efficacy of CBP-201 in adult patients with moderate to severe atopic dermatitis (CBP-201AU002). 10 CBP-201: Phase 1b – Trial Design & Primary Endpoint AE Profile Consistent with Data Reported in Studies of Existing IL-4Ra Blockers A Randomized, Double-Blind, Placebo-Controlled Multi-Centered, Dose-Escalation Trial of Safety, Pharmacokinetics and Pharmacodynamics of CBP-201 in Adult Subjects With Moderate-to-Severe Atopic Dermatitis Study conducted in 13 centers in Australia and New Zealand 4 Weeks 7 Weeks 75 mg/Placebo (4:1), Safety n=10 Follow-up • No serious adverse events (SAEs) and no injection site Screening Cohort 1 4 Weeks 7 Weeks reaction or conjunctivitis / keratitis AEs Randomization 150 mg/Placebo (4:1). Safety Baseline n=10 Follow-up • No dose proportional effect on TEAEs either by frequency Screening Cohort 2 4 Weeks 7 Weeks Randomization or severity 300 mg/Placebo (4:1), Safety Baseline n=10 Follow-up Screening • Most TEAEs were mild in severity, with the majority Cohort 3 Randomization deemed unrelated to CBP-201 Baseline • A single TEAE (atopic dermatitis flare) leading to study Primary Endpoint: (At week 11) treatment discontinuation in one subject in each of the • Safety and tolerability CBP-201 75mg and placebo groups Exploratory Efficacy Endpoints: (At week 4) • Percent change in EASI from Baseline • Proportion of patients achieving IGA of 0 or 1 (clear or almost clear) (IGA 0,1) • Change in total affected BSA from baseline BSA: Body Surface Area EASI: Eczema Area and Severity Index IGA: Investigator’s Global Assessment P-NRS: Pruritus Numeric Rating Scale • Change in P-NRS from baseline (pruritus intensity and frequency) DLQI: Dermatology Life Quality Index • A randomized, double-blind, placebo-controlled, multiple ascending dose study of the safety, pharmacokinetics and preliminary efficacy of CBP-201 in adult patients with moderate to severe atopic dermatitis (CBP-201AU002).
11 CBP-201: Phase 1b – Efficacy Results - Rapid Onset of Action Improvements in Key Physician & Patient Assessed Endpoints * EASI – Mean Change from Baseline IGA 0,1 Responders (%) Weekly Average P-NRS-Frequency Weekly Average P-NRS-Severity (%) (n=8) (n=8) (n=8) ` (n=8) Placebo CBP-201 75mg Placebo (n=8) CBP-201 75mg (n=8) Placebo CBP-201 75mg Week CBP-201 150mg(n=8) CBP-201 300mg (n=7) CBP-201 150mg(n=8) CBP-201 300mg (n=7) (n=8) (n=7) CBP-201 150mg CBP-201 300mg 0 1 2 3 4 0 60 0 1 2 3 4 0 1 2 3 4 -3.7 Week Week 10 10 -14.6 -10 4.5 3.2 50.0 -16.7 -22.3 50 0 0 -20 42.9 -7.2 -8.2 -23.3 -32.9 -3.6 -3.8 -30 -27.0 -10 -10 -17.2 -17.7 40 -21.0 -33.6 -40 -22.8 -24.2 -33.1 -50.8 -20 -20 -… -25.6 -… -39.3 -50 30 -30.7 -30.9 -23.6 -25.0 -30 -30 -26.1 -26.6 -66.1 -41.0 -60 -40.3 -57.0 -34.7 20 -40 -40 -74.0 -36.4 -36.5 -70 -37.9 -50.2 -68.5 12.5 12.512 .5 -47.4 -50 -50 -80 -74.4 -47.5 10 -46.9 -90 -60 -60 -52.8 -54.4 0 -100 -70 -70 0 1 2 3 4 (n=8) (n=8) Placebo CBP-201 75mg Week CBP-201 150mg (n=8) CBP-201 300mg (n=7) IGA 0,1 = An IGA score of 0 or 1 / P-NRS = Pruritus Numerical Rating Scale / EASI = Eczema Area and Severity Index • A randomized, double-blind, placebo-controlled, multiple ascending dose study of the safety, pharmacokinetics and preliminary efficacy of CBP-201 in adult patients with moderate to severe atopic dermatitis (CBP-201AU002). Decrease in EASI from baseline (%) IGA 0,1 Responders (%) PNRS-Frequency change from baseline (%) PNRS-Frequency change from baseline (%)11 CBP-201: Phase 1b – Efficacy Results - Rapid Onset of Action Improvements in Key Physician & Patient Assessed Endpoints * EASI – Mean Change from Baseline IGA 0,1 Responders (%) Weekly Average P-NRS-Frequency Weekly Average P-NRS-Severity (%) (n=8) (n=8) (n=8) ` (n=8) Placebo CBP-201 75mg Placebo (n=8) CBP-201 75mg (n=8) Placebo CBP-201 75mg Week CBP-201 150mg(n=8) CBP-201 300mg (n=7) CBP-201 150mg(n=8) CBP-201 300mg (n=7) (n=8) (n=7) CBP-201 150mg CBP-201 300mg 0 1 2 3 4 0 60 0 1 2 3 4 0 1 2 3 4 -3.7 Week Week 10 10 -14.6 -10 4.5 3.2 50.0 -16.7 -22.3 50 0 0 -20 42.9 -7.2 -8.2 -23.3 -32.9 -3.6 -3.8 -30 -27.0 -10 -10 -17.2 -17.7 40 -21.0 -33.6 -40 -22.8 -24.2 -33.1 -50.8 -20 -20 -… -25.6 -… -39.3 -50 30 -30.7 -30.9 -23.6 -25.0 -30 -30 -26.1 -26.6 -66.1 -41.0 -60 -40.3 -57.0 -34.7 20 -40 -40 -74.0 -36.4 -36.5 -70 -37.9 -50.2 -68.5 12.5 12.512 .5 -47.4 -50 -50 -80 -74.4 -47.5 10 -46.9 -90 -60 -60 -52.8 -54.4 0 -100 -70 -70 0 1 2 3 4 (n=8) (n=8) Placebo CBP-201 75mg Week CBP-201 150mg (n=8) CBP-201 300mg (n=7) IGA 0,1 = An IGA score of 0 or 1 / P-NRS = Pruritus Numerical Rating Scale / EASI = Eczema Area and Severity Index • A randomized, double-blind, placebo-controlled, multiple ascending dose study of the safety, pharmacokinetics and preliminary efficacy of CBP-201 in adult patients with moderate to severe atopic dermatitis (CBP-201AU002). Decrease in EASI from baseline (%) IGA 0,1 Responders (%) PNRS-Frequency change from baseline (%) PNRS-Frequency change from baseline (%)
12 CBP-201: Phase 1b – Efficacy Results Week 4 EASI-50 and IGA 0,1 (% Responders) in AD patients in Early Phase Clinical Trials For Illustrative Purposes Only:- Not a head-to-head comparison. Differences exist between trial designs and subject characteristics and caution should be exercised when comparing data across trials Proportion of patients Proportion of patients Proportion of patients Proportion of patients Proportion of patients Achieving EASI-50 Achieving EASI-50 Achieving EASI-50 Achieving IGA 0,1 Achieving IGA 0,1 2 2 1 2 1 (Week 4) (Week 4) (Week 12) (Week 4) (Week 4) EASI-50 = A 50% reduction in EASI score vs. baseline; IGA 0,1 = An IGA score of 0 or 1; EASI Score (0-72); IGA: 5-Point scale (0-4) :[Higher = Worse] for CBP-201 / 6-Point scale (0-5) for dupilumab – Scale for dupilumab of 4 or 5 (Severe or very severe) matches score of 4 for CBP-201 (Severe) 100% 100% 100% 100% 100% 100% 90% 90% 85% 90% 90% 90% 80% 80% 80% 80% 80% 69% 70% 70% 70% 70% 70% 60% 60% 60% 60% 60% 50% 50% 50% 50% 50% 43% 38% 35% 40% 40% 40% 40% 40% 30% 30% 30% 30% 30% 20% 18% 20% 20% 20% 20% 20% 13% 10% 10% 10% 10% 10% 4% 0% 0% 0% 0% 0% Placebo CBP-201 (300mg Placebo CBP-201 (300mg Placebo Dupilumab (300mg Placebo Dupilumab (300mg Placebo Dupilumab (300mg QW) QW) QW) QW) QW) (n=8) (n=7) (n=54) (n=55) (n=54) (n=55) (n=8) (n=7) (n=54) (n=55) Baseline EASI: Placebo (33.4) / CBP-201(23.2) Baseline EASI: Placebo (30.8) / Dupilumab (28.4) Baseline IGA: Placebo (3.3) / CBP-201 (3.3) Baseline IGA: Placebo (4.0) / Dupilumab (3.9) 1. A randomized, double-blind, placebo-controlled, multiple ascending dose study of the safety, pharmacokinetics and preliminary efficacy of CBP-201 in adult patients with moderate to severe atopic dermatitis (CBP-201AU002) 2. Beck LA, Thaci T, et al. N Engl J Med 2014; 371:130-13912 CBP-201: Phase 1b – Efficacy Results Week 4 EASI-50 and IGA 0,1 (% Responders) in AD patients in Early Phase Clinical Trials For Illustrative Purposes Only:- Not a head-to-head comparison. Differences exist between trial designs and subject characteristics and caution should be exercised when comparing data across trials Proportion of patients Proportion of patients Proportion of patients Proportion of patients Proportion of patients Achieving EASI-50 Achieving EASI-50 Achieving EASI-50 Achieving IGA 0,1 Achieving IGA 0,1 2 2 1 2 1 (Week 4) (Week 4) (Week 12) (Week 4) (Week 4) EASI-50 = A 50% reduction in EASI score vs. baseline; IGA 0,1 = An IGA score of 0 or 1; EASI Score (0-72); IGA: 5-Point scale (0-4) :[Higher = Worse] for CBP-201 / 6-Point scale (0-5) for dupilumab – Scale for dupilumab of 4 or 5 (Severe or very severe) matches score of 4 for CBP-201 (Severe) 100% 100% 100% 100% 100% 100% 90% 90% 85% 90% 90% 90% 80% 80% 80% 80% 80% 69% 70% 70% 70% 70% 70% 60% 60% 60% 60% 60% 50% 50% 50% 50% 50% 43% 38% 35% 40% 40% 40% 40% 40% 30% 30% 30% 30% 30% 20% 18% 20% 20% 20% 20% 20% 13% 10% 10% 10% 10% 10% 4% 0% 0% 0% 0% 0% Placebo CBP-201 (300mg Placebo CBP-201 (300mg Placebo Dupilumab (300mg Placebo Dupilumab (300mg Placebo Dupilumab (300mg QW) QW) QW) QW) QW) (n=8) (n=7) (n=54) (n=55) (n=54) (n=55) (n=8) (n=7) (n=54) (n=55) Baseline EASI: Placebo (33.4) / CBP-201(23.2) Baseline EASI: Placebo (30.8) / Dupilumab (28.4) Baseline IGA: Placebo (3.3) / CBP-201 (3.3) Baseline IGA: Placebo (4.0) / Dupilumab (3.9) 1. A randomized, double-blind, placebo-controlled, multiple ascending dose study of the safety, pharmacokinetics and preliminary efficacy of CBP-201 in adult patients with moderate to severe atopic dermatitis (CBP-201AU002) 2. Beck LA, Thaci T, et al. N Engl J Med 2014; 371:130-139
13 CBP-201: Phase 1b – Efficacy Results Reported IGA 0,1 % Responders Data of Select Biologics in Development with AD patients For Illustrative Purposes Only:- Not a head-to-head comparison. Differences exist between trial designs and subject characteristics and caution should be exercised when comparing data across trials Dosing Regimens: Proportion (%) of patients Achieving IGA 0,1 (Week 4) Phase 2b Phase 2a Phase 1• Lebrikizumab (250mg Q2W) Phase 2a Phase 2 Phase 1 Baseline IGA: 5-Point scale (0-4) for all trials except dupilumab and KHK-4083, which used a 6-point scale (0-5), with scores of 4 & 5 matching scores of 4 from other trials • Bermekimab (400mg QW) 3.4 3.3 3.4 3.8 3.3 3.4 4.0 3.9 3.3 3.3 • KHK-4083 (10mg/kg IV, Q2W) 43 • GBR-830 (10mg/kg IV, Q4W) • Dupilumab (300mg QW) • CBP-201 (300mg QW) • Lebrikizumab: An IL-13 antibody developed by Roche and Dermira, acquired by Eli Lily in 2020 18 • Bermekimab: an IL-1a antibody developed by 14 14 14 13 XBiotech, acquired by Janssen at end of 2019 • KHK-4083: Fully humanized anti-OX40 5.1 4 monoclonal antibody developed by Kyowa Kirin 0 0 • GBR-830: Humanized anti-OX40 monoclonal 1 2 3 4 5 6 Placebo Lebrikizumab Bermekimab KHK-4083 Placebo GBR-830 Placebo Dupilumab Placebo CBP-201 antibody developed by Glenmark / Ichnos (n=52) (n=75) (n=28) (n=22) (n=16) (n=46) (n=54) (n=55) (n=8) (n=7) 4. Guttmann-Yasky, E. et al. GBR 830, an anti-OX40, improves skin gene signatures and clinical scores in patients 1. Guttmann-Yasky, E. et al. JAMA Dermatol. doi:10.1001/jamadermatol.2020.0079 2. Simpson E. AAD, 2019. Oral Presentation with atopic dermatitis. J Allergy Clin Immunol 2019;144:482-93. https://doi.org/10.1016/j.jaci.2018.11.053 3. Nagakawa, H. et al., M. A Safety, tolerability and efficacy of repeated intravenous infusions of KHK4083, a fully human anti-OX40 monoclonal 5. Beck LA, Thaci T, et al. N Engl J Med 2014; 371:130-139 antibody, in Japanese patients with moderate to severe atopic dermatitis. Journal of Dermatological Science 99 (2020) 82–8913 CBP-201: Phase 1b – Efficacy Results Reported IGA 0,1 % Responders Data of Select Biologics in Development with AD patients For Illustrative Purposes Only:- Not a head-to-head comparison. Differences exist between trial designs and subject characteristics and caution should be exercised when comparing data across trials Dosing Regimens: Proportion (%) of patients Achieving IGA 0,1 (Week 4) Phase 2b Phase 2a Phase 1• Lebrikizumab (250mg Q2W) Phase 2a Phase 2 Phase 1 Baseline IGA: 5-Point scale (0-4) for all trials except dupilumab and KHK-4083, which used a 6-point scale (0-5), with scores of 4 & 5 matching scores of 4 from other trials • Bermekimab (400mg QW) 3.4 3.3 3.4 3.8 3.3 3.4 4.0 3.9 3.3 3.3 • KHK-4083 (10mg/kg IV, Q2W) 43 • GBR-830 (10mg/kg IV, Q4W) • Dupilumab (300mg QW) • CBP-201 (300mg QW) • Lebrikizumab: An IL-13 antibody developed by Roche and Dermira, acquired by Eli Lily in 2020 18 • Bermekimab: an IL-1a antibody developed by 14 14 14 13 XBiotech, acquired by Janssen at end of 2019 • KHK-4083: Fully humanized anti-OX40 5.1 4 monoclonal antibody developed by Kyowa Kirin 0 0 • GBR-830: Humanized anti-OX40 monoclonal 1 2 3 4 5 6 Placebo Lebrikizumab Bermekimab KHK-4083 Placebo GBR-830 Placebo Dupilumab Placebo CBP-201 antibody developed by Glenmark / Ichnos (n=52) (n=75) (n=28) (n=22) (n=16) (n=46) (n=54) (n=55) (n=8) (n=7) 4. Guttmann-Yasky, E. et al. GBR 830, an anti-OX40, improves skin gene signatures and clinical scores in patients 1. Guttmann-Yasky, E. et al. JAMA Dermatol. doi:10.1001/jamadermatol.2020.0079 2. Simpson E. AAD, 2019. Oral Presentation with atopic dermatitis. J Allergy Clin Immunol 2019;144:482-93. https://doi.org/10.1016/j.jaci.2018.11.053 3. Nagakawa, H. et al., M. A Safety, tolerability and efficacy of repeated intravenous infusions of KHK4083, a fully human anti-OX40 monoclonal 5. Beck LA, Thaci T, et al. N Engl J Med 2014; 371:130-139 antibody, in Japanese patients with moderate to severe atopic dermatitis. Journal of Dermatological Science 99 (2020) 82–89
TRIAL FULLY 14 CBP-201: Global Phase 2b AD Trial Design ENROLLED Trial designed for dose-ranging, maximal efficacy and possible longer dosing interval (NCT04444752) A Randomized, Double-Blind, Placebo-Controlled Multi-Centered Trial of the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of CBP-201 in Adult Subjects With Moderate-to-Severe Atopic Dermatitis CBP-201, 600 mg LD D1 + 300 mg Q2W, n=55 Follow-up Randomization CBP-201, 600 mg LD D1 + 150 mg Q2W, n=55 Follow-up 1:1:1:1 n=220 CBP-201, 600 mg LD D1 + 300 mg Q4W, n=55 Follow-up Placebo, n=55 Follow-up Screening/30 Days 16 Weeks/Treatment 8 Weeks Key Inclusion Criteria: Primary Endpoints • Adults with moderate-to-severe AD inadequately controlled with topical • Percent change in EASI from Baseline to W16 corticosteroids and calcineurin inhibitors Exploratory Efficacy Endpoints: • Having atopic dermatitis for ≥ 1 y • EASI ≥16• Proportion of patients achieving IGA 0,1 at Week 16 • Proportion of patients achieving EASI-75 at Week 16 • IGA score ≥3 (5-point scale [0-4]) • Proportion of patients achieving EASI-90 at Week 16 • ≥10% BSA involvement • Change in P-NRS from Baseline to Week 16TRIAL FULLY 14 CBP-201: Global Phase 2b AD Trial Design ENROLLED Trial designed for dose-ranging, maximal efficacy and possible longer dosing interval (NCT04444752) A Randomized, Double-Blind, Placebo-Controlled Multi-Centered Trial of the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of CBP-201 in Adult Subjects With Moderate-to-Severe Atopic Dermatitis CBP-201, 600 mg LD D1 + 300 mg Q2W, n=55 Follow-up Randomization CBP-201, 600 mg LD D1 + 150 mg Q2W, n=55 Follow-up 1:1:1:1 n=220 CBP-201, 600 mg LD D1 + 300 mg Q4W, n=55 Follow-up Placebo, n=55 Follow-up Screening/30 Days 16 Weeks/Treatment 8 Weeks Key Inclusion Criteria: Primary Endpoints • Adults with moderate-to-severe AD inadequately controlled with topical • Percent change in EASI from Baseline to W16 corticosteroids and calcineurin inhibitors Exploratory Efficacy Endpoints: • Having atopic dermatitis for ≥ 1 y • EASI ≥16• Proportion of patients achieving IGA 0,1 at Week 16 • Proportion of patients achieving EASI-75 at Week 16 • IGA score ≥3 (5-point scale [0-4]) • Proportion of patients achieving EASI-90 at Week 16 • ≥10% BSA involvement • Change in P-NRS from Baseline to Week 16
TRIAL 15 CBP-201: Global Phase 2b Asthma Trial Design ONGOING Trial designed for dose-ranging (NCT04773678) A Multi-center, Randomized, Double-blind, Parallel Group, Placebo-controlled, Efficacy and Safety Study of CBP-201 in Patients With Moderate to Severe Persistent Asthma With Type 2 Inflammation CBP-201, 600 mg LD D1 + 150 mg Q2W, n=100 Follow-up Randomization CBP-201, 600 mg LD D1 + 300 mg Q2W, n=100 Follow-up 1:1:1 n=300 Placebo, n=100 Follow-up Screening/run in 28 Days 24 Weeks/Treatment 8 Weeks Key Inclusion Criteria Primary Endpoints • Moderate to severe uncontrolled asthma • Change from Baseline in FEV1 at Week 12 ‒ Existing treatment with medium to high dose in combination with a second Secondary Efficacy Endpoints reliever/controller (eg, LABA, LTRA, LAMA, or theophylline) for at least 3 months with a stable dose ≥1 month prior to the screening visit • Change from Baseline in lung function at other timepoints ‒ Pre-bronchodilator FEV1 40 to 85% of predicted normal at Visits 1 and 2, prior to • Exacerbation of asthma randomization • PROs (ACQ-6, symptom diary) ‒ Screening blood eosinophil count ≥150 cells/μL ‒ ACQ-6 score ≥1.5 at Visits 1 and 2, prior to randomization • PD markers (FENO, eosinophils, ECP, periostin, TARC) • At least 1 documented asthma exacerbations in the 12 months prior to the • Rescue medication use date informed consent that required use of a systemic corticosteroid ACQ-6 :Asthma Control Questionnaire 6-question version; FENO: Fractional Exhaled Nitric Oxide; FEV1: Forced expiratory volume at 1 second.TRIAL 15 CBP-201: Global Phase 2b Asthma Trial Design ONGOING Trial designed for dose-ranging (NCT04773678) A Multi-center, Randomized, Double-blind, Parallel Group, Placebo-controlled, Efficacy and Safety Study of CBP-201 in Patients With Moderate to Severe Persistent Asthma With Type 2 Inflammation CBP-201, 600 mg LD D1 + 150 mg Q2W, n=100 Follow-up Randomization CBP-201, 600 mg LD D1 + 300 mg Q2W, n=100 Follow-up 1:1:1 n=300 Placebo, n=100 Follow-up Screening/run in 28 Days 24 Weeks/Treatment 8 Weeks Key Inclusion Criteria Primary Endpoints • Moderate to severe uncontrolled asthma • Change from Baseline in FEV1 at Week 12 ‒ Existing treatment with medium to high dose in combination with a second Secondary Efficacy Endpoints reliever/controller (eg, LABA, LTRA, LAMA, or theophylline) for at least 3 months with a stable dose ≥1 month prior to the screening visit • Change from Baseline in lung function at other timepoints ‒ Pre-bronchodilator FEV1 40 to 85% of predicted normal at Visits 1 and 2, prior to • Exacerbation of asthma randomization • PROs (ACQ-6, symptom diary) ‒ Screening blood eosinophil count ≥150 cells/μL ‒ ACQ-6 score ≥1.5 at Visits 1 and 2, prior to randomization • PD markers (FENO, eosinophils, ECP, periostin, TARC) • At least 1 documented asthma exacerbations in the 12 months prior to the • Rescue medication use date informed consent that required use of a systemic corticosteroid ACQ-6 :Asthma Control Questionnaire 6-question version; FENO: Fractional Exhaled Nitric Oxide; FEV1: Forced expiratory volume at 1 second.
TRIAL 16 CBP-201: Global Phase 2b CRSwNP Trial Design ONGOING Trial designed for dose-ranging, maximal efficacy and possible longer dosing interval (NCT04783389) A multi-center, randomized, double-blind, placebo-controlled study to evaluate the effect of CBP-201 on a background of mometasone furoate nasal spray (MFNS) in reducing endoscopic nasal polyp score (NPS) and nasal congestion/obstruction score (NCS) severity in eligible patients with CRSwNP whose disease remains inadequately controlled despite daily treatment with intranasal corticosteroid (INCS) therapy in comparison to placebo CBP-201, 600 mg LD D1 + 300 mg Q2W, n=49 Follow-up Randomization CBP-201, 600 mg LD D1 + 300 mg Q4W, n=49 Follow-up 1:1:1 n=147 Placebo, n=49 Follow-up Screening/run in 28 Days 24 Weeks/Treatment 8 Weeks Key Inclusion Criteria Co-Primary Efficacy Endpoints • Chronic rhinosinusitis patients with large bilateral nasal polyps that • Change from baseline at week 24 in endoscopic Nasal Polyp Score remain uncontrolled despite daily treatment with intranasal CS • Change from baseline at week 24 in Nasal Congestion Score Other Population Details Secondary Efficacy Endpoints • 50% Co-morbid asthma • PRO (SNOT-22, Total Nasal Sinus Score, Patient Symptom Diary, Smell Testing/UPSIT, Visual • Allowing patients who have had prior surgery and those who have not had Analog Scale for Rhinosinusitus) prior surgery for NP • CT Assessments (Lund-MacKay score and sinus volume measures) • Respiratory Physiology (Nasal Peak Inspiratory Flow) • Rescue Tx use and time to Rescue TxTRIAL 16 CBP-201: Global Phase 2b CRSwNP Trial Design ONGOING Trial designed for dose-ranging, maximal efficacy and possible longer dosing interval (NCT04783389) A multi-center, randomized, double-blind, placebo-controlled study to evaluate the effect of CBP-201 on a background of mometasone furoate nasal spray (MFNS) in reducing endoscopic nasal polyp score (NPS) and nasal congestion/obstruction score (NCS) severity in eligible patients with CRSwNP whose disease remains inadequately controlled despite daily treatment with intranasal corticosteroid (INCS) therapy in comparison to placebo CBP-201, 600 mg LD D1 + 300 mg Q2W, n=49 Follow-up Randomization CBP-201, 600 mg LD D1 + 300 mg Q4W, n=49 Follow-up 1:1:1 n=147 Placebo, n=49 Follow-up Screening/run in 28 Days 24 Weeks/Treatment 8 Weeks Key Inclusion Criteria Co-Primary Efficacy Endpoints • Chronic rhinosinusitis patients with large bilateral nasal polyps that • Change from baseline at week 24 in endoscopic Nasal Polyp Score remain uncontrolled despite daily treatment with intranasal CS • Change from baseline at week 24 in Nasal Congestion Score Other Population Details Secondary Efficacy Endpoints • 50% Co-morbid asthma • PRO (SNOT-22, Total Nasal Sinus Score, Patient Symptom Diary, Smell Testing/UPSIT, Visual • Allowing patients who have had prior surgery and those who have not had Analog Scale for Rhinosinusitus) prior surgery for NP • CT Assessments (Lund-MacKay score and sinus volume measures) • Respiratory Physiology (Nasal Peak Inspiratory Flow) • Rescue Tx use and time to Rescue Tx
CBP-307: A next generation selective sphingosine 1-phosphate receptor 1 modulator (S1P1) in development for IBDCBP-307: A next generation selective sphingosine 1-phosphate receptor 1 modulator (S1P1) in development for IBD
18 CBP-307: A Next Generation S1P1 Modulator Mechanism of Action – S1P1 Modulator – A validated target • Blocking T Cell Egress from Lymph Nodes Reduces Inflammation Implicated in Many T cell-mediated 1 diseases • S1P1 mediates T cell movement from lymph nodes into circulation, and hence migration to tissues to release inflammatory mediators • CBP-307 internalizes S1P1, trapping T cells inside lymph nodes • Potential for differentiation based on observations of ‒ High Potency & Selectivity • Designed to be the most potent modulator of S1P1 drug class, if approved • No significant activity for S1P3, a receptor subtype associated with known safety concerns • Significantly lower potency for S1P4 and S1P5, than S1P1 ‒ Remain able to select phase 3 dose in both UC & CD for optimal effects • Potential for clinical results to show ‒ Once daily dosing, with fast onset and offset of action ‒ Greater clinical response S1P1 Sphingosine 1-phosphate-receptor 1 ‒ Safety profile consistent with second generation S1P1 1. Krause, A. et al. Modeling clinical efficacy of the S1P receptor modulator ponesimod in Psoriasis. Journal of Dermatological Science 89 (2018) 136–14518 CBP-307: A Next Generation S1P1 Modulator Mechanism of Action – S1P1 Modulator – A validated target • Blocking T Cell Egress from Lymph Nodes Reduces Inflammation Implicated in Many T cell-mediated 1 diseases • S1P1 mediates T cell movement from lymph nodes into circulation, and hence migration to tissues to release inflammatory mediators • CBP-307 internalizes S1P1, trapping T cells inside lymph nodes • Potential for differentiation based on observations of ‒ High Potency & Selectivity • Designed to be the most potent modulator of S1P1 drug class, if approved • No significant activity for S1P3, a receptor subtype associated with known safety concerns • Significantly lower potency for S1P4 and S1P5, than S1P1 ‒ Remain able to select phase 3 dose in both UC & CD for optimal effects • Potential for clinical results to show ‒ Once daily dosing, with fast onset and offset of action ‒ Greater clinical response S1P1 Sphingosine 1-phosphate-receptor 1 ‒ Safety profile consistent with second generation S1P1 1. Krause, A. et al. Modeling clinical efficacy of the S1P receptor modulator ponesimod in Psoriasis. Journal of Dermatological Science 89 (2018) 136–145
19 CBP-307: Pre-Clinical Highly selective for S1P1, with up to 80,000-fold selectivity for S1P1 vs. S1P3 High selectivity for S1P1 EC (nM) 50 Name S1P1 S1P2 S1P3 S1P4 S1P5 1 1 2 2 2 2 CBP-307 0.09 >10,000 7,900 19 3.97 3 Ozanimod 2.99 >10,000 >10,000 >10,000 29.32 (CC-1122273) Etrasimod 6.10 >10,000 >10,000 147 24.4 4 (APD334) 1. cAMP Assay 2. β-Arrestin Assay 3. NDA 2-9-899 (Ozanimod, RPC1063) Non-Clinical Review - Table 2. Center for Drug Evaluation and Research. 209899Orig1s000PharmR.pdf (fda.govhttps://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/209899Orig1s000PharmR.pdf 4. Buzard, D.J., Kim, S.H. et al. Discovery of APD334. Design of a Clinical Stage Functional Antagonist of the Sphingosine-1-phosphate-1 Receptor. ACS Medicinal Chemistry Letters, 2014; 5(12); 1313-1317 - β-Arrestin Assay 19 CBP-307: Pre-Clinical Highly selective for S1P1, with up to 80,000-fold selectivity for S1P1 vs. S1P3 High selectivity for S1P1 EC (nM) 50 Name S1P1 S1P2 S1P3 S1P4 S1P5 1 1 2 2 2 2 CBP-307 0.09 >10,000 7,900 19 3.97 3 Ozanimod 2.99 >10,000 >10,000 >10,000 29.32 (CC-1122273) Etrasimod 6.10 >10,000 >10,000 147 24.4 4 (APD334) 1. cAMP Assay 2. β-Arrestin Assay 3. NDA 2-9-899 (Ozanimod, RPC1063) Non-Clinical Review - Table 2. Center for Drug Evaluation and Research. 209899Orig1s000PharmR.pdf (fda.govhttps://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/209899Orig1s000PharmR.pdf 4. Buzard, D.J., Kim, S.H. et al. Discovery of APD334. Design of a Clinical Stage Functional Antagonist of the Sphingosine-1-phosphate-1 Receptor. ACS Medicinal Chemistry Letters, 2014; 5(12); 1313-1317 - β-Arrestin Assay
20 CBP-307: Phase 1 – PK / PD Profile Supports QD Dosing, Rapid Onset of Action, Strong PD effect and Rapid Offset on Drug Discontinuation • Oral, 25-hour half-life supports QD dosing • Rapid 50% ALC reduction by day 7, with steady-state by day 14 • Rapid washout after discontinuation correlates with a more rapid • Steady-state ALC reduction of 65-75% correlates with strong recovery of lymphocyte levels efficacy potential • Not a pro-drug and does not require in vivo conversion to produce • Rapid ALC recovery to baseline within 7 days post-discontinuation its effects • Well tolerated, with observed AE consistent with those reported in trials of other S1P1 modulators Absolute Lymphocyte Count (ALC) Drug Name T½ h (days) Lymphocyte Recovery Time 40 (% Reduction from Baseline) 20 Fingolimod (0.5 mg, QD) ~216h (6-9d) 30-60d 0 1,2 MT-1303 (0.4 mg, QD) 451h (19d) >48d -20 -40 Ozanimod (1 mg, QD) ~264h >7d (CC1122373) (11d) (no report beyond this time) -60 -70% 3 -80 Etrasimod (2 mg, QD) 35h (1.5d) <7d -100 0 7 14 21 28 35 42 CBP-307 (0.25 mg, QD) 25h (1d) <7d Study Day placebo 0.15 mg 0.25 mg (n=4) (n=6) (n=6) 1. Kifuji, T et al. https://www.tandfonline.com/doi/abs/10.1080/00498254.2018.1525508?journalCode=ixen20 [Accessed August 1st, 2020] th 2. Sugahara, K et al. https://bpspubs.onlinelibrary.wiley.com/doi/epdf/10.1111/bph.13641 . British Journal of Pharmacology (2017) 174 15–27. [Accessed December 16 , 2020] 3. DOP078 Pharmacology and safety of etrasimod (APD334), an oral, potent, next-generation, selective S1P receptor modulator. T. Kühbacher, R. et al. Journal of Crohn's and Colitis, Volume 11, Issue suppl_1, February 2017, Page S72. https://academic.oup.com/ecco-jcc/article/11/suppl_1/S72/2960933. https://doi.org/10.1093/ecco-jcc/jjx002.11520 CBP-307: Phase 1 – PK / PD Profile Supports QD Dosing, Rapid Onset of Action, Strong PD effect and Rapid Offset on Drug Discontinuation • Oral, 25-hour half-life supports QD dosing • Rapid 50% ALC reduction by day 7, with steady-state by day 14 • Rapid washout after discontinuation correlates with a more rapid • Steady-state ALC reduction of 65-75% correlates with strong recovery of lymphocyte levels efficacy potential • Not a pro-drug and does not require in vivo conversion to produce • Rapid ALC recovery to baseline within 7 days post-discontinuation its effects • Well tolerated, with observed AE consistent with those reported in trials of other S1P1 modulators Absolute Lymphocyte Count (ALC) Drug Name T½ h (days) Lymphocyte Recovery Time 40 (% Reduction from Baseline) 20 Fingolimod (0.5 mg, QD) ~216h (6-9d) 30-60d 0 1,2 MT-1303 (0.4 mg, QD) 451h (19d) >48d -20 -40 Ozanimod (1 mg, QD) ~264h >7d (CC1122373) (11d) (no report beyond this time) -60 -70% 3 -80 Etrasimod (2 mg, QD) 35h (1.5d) <7d -100 0 7 14 21 28 35 42 CBP-307 (0.25 mg, QD) 25h (1d) <7d Study Day placebo 0.15 mg 0.25 mg (n=4) (n=6) (n=6) 1. Kifuji, T et al. https://www.tandfonline.com/doi/abs/10.1080/00498254.2018.1525508?journalCode=ixen20 [Accessed August 1st, 2020] th 2. Sugahara, K et al. https://bpspubs.onlinelibrary.wiley.com/doi/epdf/10.1111/bph.13641 . British Journal of Pharmacology (2017) 174 15–27. [Accessed December 16 , 2020] 3. DOP078 Pharmacology and safety of etrasimod (APD334), an oral, potent, next-generation, selective S1P receptor modulator. T. Kühbacher, R. et al. Journal of Crohn's and Colitis, Volume 11, Issue suppl_1, February 2017, Page S72. https://academic.oup.com/ecco-jcc/article/11/suppl_1/S72/2960933. https://doi.org/10.1093/ecco-jcc/jjx002.115
21 CBP-307: Phase 1 – PK / PD Profile Oral, QD Dosing, similar onset and offset of action to etrasimod and faster offset vs. ozanimod, in HV For Illustrative Purposes Only:- Not a head-to-head comparison. Differences exist between trial designs and subject characteristics and caution should be exercised when comparing data across trials Mean percent change in absolute lymphocyte count (% reduction from baseline) 1 2,3 Ozanimod Etrasimod CBP-307 40 40 40 Dosing period Follow-up Dosing period Follow-up Dosing period Follow-up 20 20 20 0 0 0 -20 -20 -20 -40 -40 -40 -60 -60 -60 -70% -80 -80 -80 -100 -100 -100 0 7 14 21 28 0 7 14 21 28 35 42 0 7 14 21 28 35 42 Study Day Study Day Study Day Placebo 2.0mg Placebo 2.0mg Placebo 0.15mg 0.25mg (n=2) (n=6) (n=10) (n=10) (n=4) (n=6) (n=6) T½ h (days) Lymphocyte Recovery Time T½ h (days) Lymphocyte Recovery Time T½ h (days) Lymphocyte Recovery Time 4 4 3 1 35h (1.5d) <7d ~264h (11d) >7d (no report beyond this time) 25h (1d) <7d 1. Tran et al. The Journal of Clinical Pharmacology 2017, 57(8) 988–996. 4. Tran et al. Advances in Therapy 2020; 37:4381–4395 5. T. Kühbacher, R. et al. Journal of Crohn's and Colitis, Volume 11, Issue suppl_1, February 2017, Page S72. 2. Peyrin-Biroulet et al. ECCO 2018 Vienna P573. 3. Ozanimod Active Metabolite. Arena corporate presentation 2018. https://academic.oup.com/ecco-jcc/article/11/suppl_1/S72/2960933. https://doi.org/10.1093/ecco-jcc/jjx002.115 https://sec.report/Document/0001564590-18-020796/ Percentage change Percentage change Percentage change21 CBP-307: Phase 1 – PK / PD Profile Oral, QD Dosing, similar onset and offset of action to etrasimod and faster offset vs. ozanimod, in HV For Illustrative Purposes Only:- Not a head-to-head comparison. Differences exist between trial designs and subject characteristics and caution should be exercised when comparing data across trials Mean percent change in absolute lymphocyte count (% reduction from baseline) 1 2,3 Ozanimod Etrasimod CBP-307 40 40 40 Dosing period Follow-up Dosing period Follow-up Dosing period Follow-up 20 20 20 0 0 0 -20 -20 -20 -40 -40 -40 -60 -60 -60 -70% -80 -80 -80 -100 -100 -100 0 7 14 21 28 0 7 14 21 28 35 42 0 7 14 21 28 35 42 Study Day Study Day Study Day Placebo 2.0mg Placebo 2.0mg Placebo 0.15mg 0.25mg (n=2) (n=6) (n=10) (n=10) (n=4) (n=6) (n=6) T½ h (days) Lymphocyte Recovery Time T½ h (days) Lymphocyte Recovery Time T½ h (days) Lymphocyte Recovery Time 4 4 3 1 35h (1.5d) <7d ~264h (11d) >7d (no report beyond this time) 25h (1d) <7d 1. Tran et al. The Journal of Clinical Pharmacology 2017, 57(8) 988–996. 4. Tran et al. Advances in Therapy 2020; 37:4381–4395 5. T. Kühbacher, R. et al. Journal of Crohn's and Colitis, Volume 11, Issue suppl_1, February 2017, Page S72. 2. Peyrin-Biroulet et al. ECCO 2018 Vienna P573. 3. Ozanimod Active Metabolite. Arena corporate presentation 2018. https://academic.oup.com/ecco-jcc/article/11/suppl_1/S72/2960933. https://doi.org/10.1093/ecco-jcc/jjx002.115 https://sec.report/Document/0001564590-18-020796/ Percentage change Percentage change Percentage change
22 CBP-307: Phase 1 – Safety Results – Generally Well-Tolerated No Unexpected Adverse Events • Once daily doses of up to 0.3 mg of CBP-307 were generally well-tolerated. • Most frequent AEs across all dose regimens included ‒ Low white blood cells ‒ Headache • Most AEs were mild or moderate • No clinically significant changes in lung function, a range of ophthalmological tests, or blood pressure • Consistent with clinical trials of other S1P1 modulators, a dose-dependent decrease in heart rate was observed early in all dose regimens.22 CBP-307: Phase 1 – Safety Results – Generally Well-Tolerated No Unexpected Adverse Events • Once daily doses of up to 0.3 mg of CBP-307 were generally well-tolerated. • Most frequent AEs across all dose regimens included ‒ Low white blood cells ‒ Headache • Most AEs were mild or moderate • No clinically significant changes in lung function, a range of ophthalmological tests, or blood pressure • Consistent with clinical trials of other S1P1 modulators, a dose-dependent decrease in heart rate was observed early in all dose regimens.
TRIAL 23 CBP-307: Global Phase 2 Trial in Moderate-to-Severe UC ONGOING CBP-307CN002 - Trial Design – 52-Week Study (Induction / Maintenance / Follow-Up) (NCT04700449) A Randomized, Double-blind, Placebo Controlled Trial to Evaluate the Efficacy and Safety of CBP-307 in Patients With Moderate to Severe Ulcerative Colitis (UC) STAGE 1 - INDUCTION PHASE (12-WEEK) STAGE 2 - MAINTENANCE PHASE (36-WEEK, DOUBLE BLIND) CBP-307 (n=65) CBP-307 0.2mg, QD, PO 0.2mg, QD, PO CBP-307 (n=65) CBP-307 0.1mg, QD, PO 0.1mg, QD, PO Placebo (n=65) Placebo Baseline Week 12 Week 24 * Week 48 Week 52 Non-responders at week 12, receive Open-Label CBP-307, 0.2mg, QD, PO * Patients who did not achieve clinical response at week 24 in Sub-Study 1, were withdrawn from treatment • Key efficacy measure: Clinical response rate at week 12 in 0.2 mg CBP-307 group versus PBO (clinical response is defined as a decrease of ≥ 3 points and ≥ 30% from baseline in the complete Mayo score, accompanied by a decrease of ≥ 1 point from baseline in the rectal bleeding sub-score or an absolute rectal bleeding sub-score of ≤ 1 point) • A Study Assessing the Efficacy and Safety of CBP-307 in Subjects With Moderate to Severe Ulcerative Colitis (UC) Screen Randomize (n=195 1:1:1) RESPONSE ASSESSED Responders SAFETY FOLLOW-UP STUDY ENDTRIAL 23 CBP-307: Global Phase 2 Trial in Moderate-to-Severe UC ONGOING CBP-307CN002 - Trial Design – 52-Week Study (Induction / Maintenance / Follow-Up) (NCT04700449) A Randomized, Double-blind, Placebo Controlled Trial to Evaluate the Efficacy and Safety of CBP-307 in Patients With Moderate to Severe Ulcerative Colitis (UC) STAGE 1 - INDUCTION PHASE (12-WEEK) STAGE 2 - MAINTENANCE PHASE (36-WEEK, DOUBLE BLIND) CBP-307 (n=65) CBP-307 0.2mg, QD, PO 0.2mg, QD, PO CBP-307 (n=65) CBP-307 0.1mg, QD, PO 0.1mg, QD, PO Placebo (n=65) Placebo Baseline Week 12 Week 24 * Week 48 Week 52 Non-responders at week 12, receive Open-Label CBP-307, 0.2mg, QD, PO * Patients who did not achieve clinical response at week 24 in Sub-Study 1, were withdrawn from treatment • Key efficacy measure: Clinical response rate at week 12 in 0.2 mg CBP-307 group versus PBO (clinical response is defined as a decrease of ≥ 3 points and ≥ 30% from baseline in the complete Mayo score, accompanied by a decrease of ≥ 1 point from baseline in the rectal bleeding sub-score or an absolute rectal bleeding sub-score of ≤ 1 point) • A Study Assessing the Efficacy and Safety of CBP-307 in Subjects With Moderate to Severe Ulcerative Colitis (UC) Screen Randomize (n=195 1:1:1) RESPONSE ASSESSED Responders SAFETY FOLLOW-UP STUDY END
TRIAL 24 CBP-307: Global Phase 2 Trial in Moderate-to-Severe UC ONGOING CBP-307CN002 - Trial Design – 52-Week Study (Induction / Maintenance / Follow-Up) (NCT04700449) A Randomized, Double-blind, Placebo Controlled Trial to Evaluate the Efficacy and Safety of CBP-307 in Patients With Moderate to Severe Ulcerative Colitis (UC) STAGE 1 - INDUCTION PHASE (12-WEEK) STAGE 2 - MAINTENANCE PHASE (36-WEEK, DOUBLE BLIND) CBP-307 (n=52) CBP-307 0.2mg, QD, PO 0.2mg, QD, PO Placebo (n=52) Placebo Baseline Week 12 Week 24 * Week 48 Week 52 Non-responders at week 12, receive Open-Label CBP-307, 0.2mg, QD, PO * Patients who did not achieve clinical response at week 24 in Sub-Study 1, were withdrawn from treatment • Key efficacy measure: Change from baseline in modified Mayo Score at Week 12 in 0.2 mg CBP-307 group versus placebo • A Study Assessing the Efficacy and Safety of CBP-307 in Subjects With Moderate to Severe Ulcerative Colitis (UC) Screen Randomize (n=104 1:1) RESPONSE ASSESSED Responders SAFETY FOLLOW-UP STUDY ENDTRIAL 24 CBP-307: Global Phase 2 Trial in Moderate-to-Severe UC ONGOING CBP-307CN002 - Trial Design – 52-Week Study (Induction / Maintenance / Follow-Up) (NCT04700449) A Randomized, Double-blind, Placebo Controlled Trial to Evaluate the Efficacy and Safety of CBP-307 in Patients With Moderate to Severe Ulcerative Colitis (UC) STAGE 1 - INDUCTION PHASE (12-WEEK) STAGE 2 - MAINTENANCE PHASE (36-WEEK, DOUBLE BLIND) CBP-307 (n=52) CBP-307 0.2mg, QD, PO 0.2mg, QD, PO Placebo (n=52) Placebo Baseline Week 12 Week 24 * Week 48 Week 52 Non-responders at week 12, receive Open-Label CBP-307, 0.2mg, QD, PO * Patients who did not achieve clinical response at week 24 in Sub-Study 1, were withdrawn from treatment • Key efficacy measure: Change from baseline in modified Mayo Score at Week 12 in 0.2 mg CBP-307 group versus placebo • A Study Assessing the Efficacy and Safety of CBP-307 in Subjects With Moderate to Severe Ulcerative Colitis (UC) Screen Randomize (n=104 1:1) RESPONSE ASSESSED Responders SAFETY FOLLOW-UP STUDY END
25 CBP-307: Phase 2 Trial in Moderate-to-Severe CD (Ended) CBP-307CN003 – Results - Generally well-tolerated with clear evidence of clinical response % of patients with any reduction in the specified endpoint at week 12 vs. • Due to the COVID-19 pandemic, this trial was ended early baseline with only 22 patients completing 12 weeks of dosing 100% 100% 100% 100% 100% 90% • Preliminary Safety Results (Safety Analysis Dataset, n=22) 80% ‒ CBP-307 was generally well-tolerated 70% ‒ Safety profile consistent with phase 1 studies and data 67% CBP-307, 0.2mg 60% reported in trials of other S1P1 modulators in development 57% Placebo for IBD 50% 40% • Preliminary Efficacy Results (Per Protocol 30% Dataset, n=18) 20% ‒ Evidence observed of clinical response with CBP-307 0.2 mg 17% 10% 0% 0% FCP ALC CDAI FCP+ALC+CDAI • Based on this data, we are advancing CBP-307 in IBD with (n=5) (n=6) (n=5) (n=6) (n=5) (n=7) (n=5) (n=7) the ongoing UC clinical trial and are planning a further clinical trial of CBP-307 in CD25 CBP-307: Phase 2 Trial in Moderate-to-Severe CD (Ended) CBP-307CN003 – Results - Generally well-tolerated with clear evidence of clinical response % of patients with any reduction in the specified endpoint at week 12 vs. • Due to the COVID-19 pandemic, this trial was ended early baseline with only 22 patients completing 12 weeks of dosing 100% 100% 100% 100% 100% 90% • Preliminary Safety Results (Safety Analysis Dataset, n=22) 80% ‒ CBP-307 was generally well-tolerated 70% ‒ Safety profile consistent with phase 1 studies and data 67% CBP-307, 0.2mg 60% reported in trials of other S1P1 modulators in development 57% Placebo for IBD 50% 40% • Preliminary Efficacy Results (Per Protocol 30% Dataset, n=18) 20% ‒ Evidence observed of clinical response with CBP-307 0.2 mg 17% 10% 0% 0% FCP ALC CDAI FCP+ALC+CDAI • Based on this data, we are advancing CBP-307 in IBD with (n=5) (n=6) (n=5) (n=6) (n=5) (n=7) (n=5) (n=7) the ongoing UC clinical trial and are planning a further clinical trial of CBP-307 in CD
CBP-174: A novel, peripherally-restricted, Histamine Receptor-3 (H3R) antagonist in development for pruritus associated with inflammatory skin diseaseCBP-174: A novel, peripherally-restricted, Histamine Receptor-3 (H3R) antagonist in development for pruritus associated with inflammatory skin disease
27 Chronic Pruritis Associated with Atopic Dermatitis (AD) Remains underserved with no approved treatments for chronic pruritus associated with inflammation Chronic pruritus associated with AD can significantly impact quality of life with patients often suffering from generalized anxiety, depression, agitation, and difficulty in concentrating and sleeping Up to 91% 40-50% of AD sufferers have of AD patients have inadequate relief of Chronic Pruritus their pruritus despite current therapies Current Treatment Options Current Treatment Limitations • Topical and oral anti-histamines for acute pruritus• No approved therapies addressing chronic pruritus of inflammatory origin • Topical AD treatments; corticosteroids (First line), calcineurin inhibitors, crisaborole• Limited, short-term efficacy with anti-histamines (H1R) • H1R histamine blockers have CNS penetration, leading • Oral AD treatments include corticosteroids and to drowsiness baricitinib (JAK1,2 inhibitor) • Unmet efficacy needs remain with biologics for AD • Dupilumab is the only approved biologic agent27 Chronic Pruritis Associated with Atopic Dermatitis (AD) Remains underserved with no approved treatments for chronic pruritus associated with inflammation Chronic pruritus associated with AD can significantly impact quality of life with patients often suffering from generalized anxiety, depression, agitation, and difficulty in concentrating and sleeping Up to 91% 40-50% of AD sufferers have of AD patients have inadequate relief of Chronic Pruritus their pruritus despite current therapies Current Treatment Options Current Treatment Limitations • Topical and oral anti-histamines for acute pruritus• No approved therapies addressing chronic pruritus of inflammatory origin • Topical AD treatments; corticosteroids (First line), calcineurin inhibitors, crisaborole• Limited, short-term efficacy with anti-histamines (H1R) • H1R histamine blockers have CNS penetration, leading • Oral AD treatments include corticosteroids and to drowsiness baricitinib (JAK1,2 inhibitor) • Unmet efficacy needs remain with biologics for AD • Dupilumab is the only approved biologic agent
28 CBP-174: A peripherally-restricted, H3R antagonist Mechanism of Action – Antagonism of H3R, predominantly at peripheral sites Pruritus in AD is mediated by a variety of pruritogens • CBP-174 is a novel small molecular entity that is a potent antagonist of the histamine 3 receptor (H3R) • Highly selective for H3R relative to H1R, H2R and H4R • Uniquely amongst investigational H3R antagonists, has minimal blood–brain barrier penetration ‒ H3R CNS activity associated with adverse effects such as insomnia • Pre-clinical animal models suggest multiple pruritogenic mediators of pruritis are reduced by peripherally restricted H3R antagonists28 CBP-174: A peripherally-restricted, H3R antagonist Mechanism of Action – Antagonism of H3R, predominantly at peripheral sites Pruritus in AD is mediated by a variety of pruritogens • CBP-174 is a novel small molecular entity that is a potent antagonist of the histamine 3 receptor (H3R) • Highly selective for H3R relative to H1R, H2R and H4R • Uniquely amongst investigational H3R antagonists, has minimal blood–brain barrier penetration ‒ H3R CNS activity associated with adverse effects such as insomnia • Pre-clinical animal models suggest multiple pruritogenic mediators of pruritis are reduced by peripherally restricted H3R antagonists
29 CBP-174: Preclinical Results – POC in Animal Model Rapidly reduces scratching bouts in a mouse model of pruritus 200 *P<0.01 vs vehicle 150 * * • CBP-174 had a strong anti-itch effect * in mice with a rapid onset of action, within the first 30 minutes of dosing 100 50 0 Vehicle 0.03 0.1 0.3 1 CBP-174 p.o. (mg/kg) • Connect BioPharma. F-1 SEC filing. Scratching bouts / 30 minutes29 CBP-174: Preclinical Results – POC in Animal Model Rapidly reduces scratching bouts in a mouse model of pruritus 200 *P<0.01 vs vehicle 150 * * • CBP-174 had a strong anti-itch effect * in mice with a rapid onset of action, within the first 30 minutes of dosing 100 50 0 Vehicle 0.03 0.1 0.3 1 CBP-174 p.o. (mg/kg) • Connect BioPharma. F-1 SEC filing. Scratching bouts / 30 minutes
TRIAL 30 CBP-174: Phase 1a – Trial Design ONGOING First-in-human, single-center, double-blind, randomized, SAD in healthy volunteers (NCT04811469) A Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study in Healthy Subjects to Evaluate the Safety, Tolerability, and Pharmacokinetics of CBP-174 After Oral Administration Ascending dose (each patient received a single dose) Cohort 1 Cohort 2 Cohort 3 Cohort 4 Cohort 5 Cohort 6 n=8 patients per cohort CBP-174 CBP-174 CBP-174 CBP-174 CBP-174 CBP-174 0.25 mg 0.5 mg 1 mg 2 mg 4 mg 8 mg n=48 N=6 N=6 N=6 N=6 N=6 N=6 3:1 Allocation R CBP-174 : Placebo Randomization Placebo Placebo Placebo Placebo Placebo Placebo N=2 N=2 N=2 N=2 N=2 N=2 • CBP-174 be administered orally • Prespecified outcome measures for 7 days post-dosing • Study conducted in a single center in Australia NCT04811469. A Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study in Healthy Subjects to Evaluate the Safety, Tolerability, and Pharmacokinetics of CBP-174 After Oral Administration.TRIAL 30 CBP-174: Phase 1a – Trial Design ONGOING First-in-human, single-center, double-blind, randomized, SAD in healthy volunteers (NCT04811469) A Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study in Healthy Subjects to Evaluate the Safety, Tolerability, and Pharmacokinetics of CBP-174 After Oral Administration Ascending dose (each patient received a single dose) Cohort 1 Cohort 2 Cohort 3 Cohort 4 Cohort 5 Cohort 6 n=8 patients per cohort CBP-174 CBP-174 CBP-174 CBP-174 CBP-174 CBP-174 0.25 mg 0.5 mg 1 mg 2 mg 4 mg 8 mg n=48 N=6 N=6 N=6 N=6 N=6 N=6 3:1 Allocation R CBP-174 : Placebo Randomization Placebo Placebo Placebo Placebo Placebo Placebo N=2 N=2 N=2 N=2 N=2 N=2 • CBP-174 be administered orally • Prespecified outcome measures for 7 days post-dosing • Study conducted in a single center in Australia NCT04811469. A Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study in Healthy Subjects to Evaluate the Safety, Tolerability, and Pharmacokinetics of CBP-174 After Oral Administration.
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