UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM
CURRENT REPORT
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If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
| Item 2.02 | Results of Operations and Financial Condition. |
On August 5, 2021, Catalyst Biosciences, Inc., (the “Company”) issued a press release announcing its financial results for the quarter ended June 30, 2021. The full text of the press release issued in connection with the announcement is furnished as Exhibit 99.1 to this Current Report on Form 8-K.
The information set forth in this Item 2.02 (including Exhibit 99.1) is being furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended (the “Securities Act”), or the Exchange Act, regardless of any general incorporation language in such filing, except as expressly set forth by specific reference in such a filing.
| Item 7.01 | Regulation FD Disclosure. |
On August 5, 2021, the Company posted an update to its corporate presentation (the “Presentation”) on its website, ir.catalystbiosciences.com/presentations-events. A copy of the Presentation is attached hereto as Exhibit 99.2.
The information in this Item 7.01 of this Current Report on Form 8-K (including Exhibit 99.2) is being furnished and shall not be deemed “filed” for purposes of Section 18 of the Exchange Act, or otherwise subject to the liabilities of that section. The information in this Current Report shall not be deemed incorporated by reference in any filing under the Securities Act or the Exchange Act, except as expressly set forth by specific reference in such a filing.
| Item 9.01 | Financial Statements and Exhibits. |
(d) Exhibits
| Exhibit No. |
Description | |
| 99.1 | Press release dated August 5, 2021. | |
| 99.2 | Presentation slide deck. | |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document). | |
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 hereunto duly authorized.
| CATALYST BIOSCIENCES, INC. | ||||||
| Date: August 5, 2021 | /s/ Clinton Musil | |||||
| Clinton Musil | ||||||
| Chief Financial Officer | ||||||
Exhibit 99.1
Catalyst Biosciences Reports Second Quarter 2021 Operating & Financial Results and Provides a Corporate Update
SOUTH SAN FRANCISCO, Calif. – August 5, 2021 – Catalyst Biosciences, Inc. (NASDAQ: CBIO) today announced its operating and financial results for the second quarter ended June 30, 2021, and provided a corporate update.
“We continue to make progress in our complement and hemostasis programs. In complement, we are advancing the development of our SQ enhanced CFI development candidate, CB 4332, where we screened the first patient in our natural history study for CFI deficiency (“ConFIrm”). We also recently disclosed new proteases from our ProTUNE™; C3b-C4b degrader and ImmunoTUNE™; C3a-C5a degrader platforms designed to target specific disorders of the complement or inflammatory pathways,” said Nassim Usman, Ph.D., president and chief executive officer of Catalyst. “With the initiation of the ConFIrm study and our plans to enter the clinic with CB 4332 in 2022 on track, we are building a robust pipeline in complement. We also continue to make progress in our Crimson 1 Phase 3 registrational study of MarzAA, in hemophilia A or B with inhibitors as well as in our Phase 1/2 trial in other rare bleeding disorders.”
Recent Milestones
Marzeptacog alfa (activated) – MarzAA
| • | The Food and Drug Administration (FDA) has granted Fast Track Designation for MarzAA for treatment of episodic bleeding in subjects with Factor FVII deficiency in June 2021. The FDA granted the Fast Track Designation for the treatment of episodic bleeding in subjects with Hemophilia A or B with inhibitors in December 2020. |
| • | Presented four posters at the International Society for Thrombosis and Haemostasis (ISTH) 2021 Virtual Congress in July 2021. The data presented support the Company’s ongoing trials of MarzAA in hemostasis. |
Systemic Complement Program
| • | Launched the ConFIrm study with the screening of the first patient in its CFI-deficiency study in the CB 4332 program, Catalyst’s wholly-owned, first-in-class, enhanced Complement Factor I (CFI), intended for prophylactic subcutaneous (SQ) administration in individuals with CFI deficiency. The ConFIrm screening study will measure CFI levels and activity in patients who have diseases related to a CFI deficiency and who may potentially benefit from CB 4332 treatment. |
| • | Hosted a research and development day on its protease medicines platform focusing on the regulation of complement, including CB 4332. The event featured a presentation by Filomeen Haerynck, M.D., Ph.D., University of Ghent, Belgium, who discussed the clinical phenotype, current treatment landscape and unmet medical need in treating patients with complement factor I (CFI) deficiency and other complement system disorders. Members of the Catalyst management team also discussed the proteases from the Company’s degrader platforms, designed to target specific disorders of the complement and other inflammatory pathways as well as other complement programs in development. |
1
Corporate
| • | Catalyst announced that it has promoted Grant Blouse, Ph.D., to chief scientific officer and Tom Knudsen, DVM, Ph.D., to senior vice president, corporate development. Howard Levy, M.B.B.Ch, Ph.D., M.M.M., chief medical officer, announced his plan to retire and transition to a senior clinical advisor role to Catalyst. |
Expected Milestones
Systemic Complement Program
| • | Advance CB 2782-PEG, the C3 degrader for the potential treatment of dry AMD in collaboration with Biogen towards the clinic |
| • | Provide additional preclinical data supporting continued development of the C4b degrader program and other complement assets |
| • | Submit an IND and initiate global clinical trial of CB 4332 |
| • | Announce development candidates in lead discovery programs |
| • | Present PK and biomarker data for CB 4332 |
MarzAA
| • | Continue enrolling the Crimson 1 Phase 3 registrational and the Phase 1/2 trials |
| • | Submit the first Crimson 1 report to the Data and Safety Monitoring Board (DSMB) |
| • | Present PK data from the Phase 1/2 trial |
Second Quarter 2021 Results and Financial Highlights
| • | Cash, cash equivalents and short-term investments, as of June 30, 2021 were $86.5 million. |
| • | Research and development expenses were $15.4 million and $12.9 million during the three months ended June 30, 2021 and 2020, respectively, an increase of $2.5 million, or 19%. The increase was due primarily to an increase of $1.4 million in personnel and facilities costs and an increase of $1.5 million in clinical and manufacturing costs, partially offset by a decrease of $0.4 million in preclinical spending. |
| • | General and administrative expenses were $4.5 million and $4.4 million during the three months ended June 30, 2021 and 2020, respectively, an increase of $0.1 million, or 3%. This increase was due primarily to an increase of $0.3 in personnel-related costs, partially offset by $0.2 million in facilities and overhead costs. |
| • | Interest and other income (expense), net was $0.0 million and $0.1 million during the three months ended June 30, 2021 and 2020, respectively, a decrease of $0.1 million. The decrease was primarily due to a decrease in interest income on investments. |
| • | Net loss attributable to common stockholders for the three-months ended June 30, 2021 was $19.9 million, or ($0.64) per basic and diluted share, compared with $17.2 million, or ($0.96) per basic and diluted share, for the prior year period. |
| • | As of June 30, 2021, the Company had 31,349,740 shares of common stock outstanding. |
2
About Catalyst Biosciences, the Protease Medicines company
Catalyst is a research and clinical development biopharmaceutical company focused on addressing unmet medical needs in rare disorders of the complement and coagulation systems. Our protease engineering platform has generated two late-stage clinical programs, including MarzAA, a subcutaneously (SQ) administered next-generation engineered coagulation Factor VIIa (FVIIa) for the treatment of episodic bleeding in subjects with rare bleeding disorders. Our complement pipeline includes a preclinical C3-degrader program licensed to Biogen for dry age-related macular degeneration, an improved complement factor I protease for SQ replacement therapy in patients with CFI deficiency and proteases from our ProTUNE™ C3b-C4b degrader and ImmunoTUNE™ C3a-C5a degrader platforms designed to target specific disorders of the complement or inflammatory pathways as well as other complement programs in development.
Forward-Looking Statements
This press release contains forward-looking statements that involve substantial risks and uncertainties. Forward-looking statements include, without limitation, statements about the product candidates of Catalyst Biosciences, Inc. (the “Company”) and the benefits of its protease engineering platform; plans to complete the ConFIrm and ConFIdence studies and the expectation that the studies will inform opportunities to develop CB 4332; plans to submit an IND for CB 4332; plans to announce development candidates in lead discovery programs and present PK and biomarker data for CB 4332; plans to continue enrollment of the Phase 3 and Phase 1/2 trials of MarzAA; the potential markets for and advantages of the Company’s complement product candidates, including CB 2782-PEG, CB 4332 and complement degraders; plans for the Company’s collaboration with Biogen; and plans to start a clinical trial of CB 4332 in 2022.
Actual results or events could differ materially from the plans, intentions, expectations and projections disclosed in the forward-looking statements. Various important factors could cause actual results or events to differ materially, including, but not limited to, the risk that trials and studies may be delayed as a result of COVID-19, competitive products and other factors, that trials may not have satisfactory outcomes, the risk that the ConFIrm and ConFIdence trials will not validate the potential market for CB 4332; the risk Catalyst may elect to terminate or postpone ongoing development programs, including development of MarzAA or any of the Company’s complement assets; the risk that the Company will need to raise additional capital, which may not be available on faorable terms if at all; the risk that Biogen will terminate Catalyst’s agreement, and other risks described in the “Risk Factors” section of the Company’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on May 6, 2021, and in other filings with the Securities and Exchange Commission. The Company does not assume any obligation to update any forward-looking statements, except as required by law.
Contact:
Ana Kapor
Catalyst Biosciences, Inc.
investors@catbio.com
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Catalyst Biosciences, Inc.
Condensed Consolidated Balance Sheets
(In thousands, except share and per share amounts)
| June 30, 2021 | December 31, 2020 | |||||||
| (Unaudited) | ||||||||
| Assets |
||||||||
| Current assets: |
||||||||
| Cash and cash equivalents |
$ | 73,621 | $ | 30,360 | ||||
| Short-term investments |
12,902 | 48,994 | ||||||
| Accounts receivable |
1,971 | 3,313 | ||||||
| Prepaid and other current assets |
8,332 | 6,843 | ||||||
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|
|
|
|||||
| Total current assets |
96,826 | 89,510 | ||||||
| Long-term investments |
— | 2,543 | ||||||
| Other assets, noncurrent |
1,169 | 528 | ||||||
| Right-of-use assets |
3,107 | 1,832 | ||||||
| Property and equipment, net |
684 | 433 | ||||||
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|
|
|||||
| Total assets |
$ | 101,786 | $ | 94,846 | ||||
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| Liabilities and stockholders’ equity |
||||||||
| Current liabilities: |
||||||||
| Accounts payable |
$ | 1,834 | $ | 5,931 | ||||
| Accrued compensation |
2,516 | 2,476 | ||||||
| Deferred revenue |
2,038 | 1,983 | ||||||
| Other accrued liabilities |
7,366 | 6,743 | ||||||
| Operating lease liability |
1,814 | 663 | ||||||
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|
|
|||||
| Total current liabilities |
15,568 | 17,796 | ||||||
| Operating lease liability, noncurrent |
1,054 | 981 | ||||||
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|||||
| Total liabilities |
16,622 | 18,777 | ||||||
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| Stockholders’ equity: |
||||||||
| Preferred stock, $0.001 par value, 5,000,000 shares authorized; zero shares issued and outstanding |
— | — | ||||||
| Common stock, $0.001 par value, 100,000,000 shares authorized; 31,349,740 and 22,097,820 shares issued and outstanding at June 30, 2021 and December 31, 2020, respectively |
31 | 22 | ||||||
| Additional paid-in capital |
442,258 | 390,803 | ||||||
| Accumulated other comprehensive income |
2 | 5 | ||||||
| Accumulated deficit |
(357,127 | ) | (314,761 | ) | ||||
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|
|
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|||||
| Total stockholders’ equity |
85,164 | 76,069 | ||||||
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| Total liabilities and stockholders’ equity |
$ | 101,786 | $ | 94,846 | ||||
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Catalyst Biosciences, Inc.
Condensed Consolidated Statements of Operations
(In thousands, except share and per share amounts)
(Unaudited)
| Three Months Ended June 30, | Six Months Ended June 30, | |||||||||||||||
| 2021 | 2020 | 2021 | 2020 | |||||||||||||
| Revenue: |
||||||||||||||||
| License |
$ | — | $ | 23 | $ | — | $ | 15,068 | ||||||||
| Collaboration |
1,132 | 1,635 | 2,599 | 2,956 | ||||||||||||
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|||||||||
| License and collaboration revenue |
1,132 | 1,658 | 2,599 | 18,024 | ||||||||||||
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|||||||||
| Operating expenses: |
||||||||||||||||
| Cost of license |
— | 23 | — | 3,070 | ||||||||||||
| Cost of collaboration |
1,139 | 1,719 | 2,619 | 3,151 | ||||||||||||
| Research and development |
15,389 | 12,906 | 32,402 | 26,170 | ||||||||||||
| General and administrative |
4,518 | 4,371 | 9,930 | 8,062 | ||||||||||||
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|||||||||
| Total operating expenses |
21,046 | 19,019 | 44,951 | 40,453 | ||||||||||||
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|||||||||
| Loss from operations |
(19,914 | ) | (17,361 | ) | (42,352 | ) | (22,429 | ) | ||||||||
| Interest and other income (expense), net |
(14 | ) | 113 | (14 | ) | 1,128 | ||||||||||
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| Net loss |
$ | (19,928 | ) | $ | (17,248 | ) | $ | (42,366 | ) | $ | (21,301 | ) | ||||
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| Net loss per share attributable to common stockholders, basic and diluted |
$ | (0.64 | ) | $ | (0.96 | ) | $ | (1.42 | ) | $ | (1.31 | ) | ||||
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| Shares used to compute net loss per share attributable to common stockholders, basic and diluted |
31,348,602 | 17,891,475 | 29,875,202 | 16,241,963 | ||||||||||||
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5
CATALYST BIOSCIENCES Corporate Overview 5 August 2021 Exhibit 99.2
Forward looking statements Certain information contained in this presentation and statements made orally during this presentation include forward-looking statements that involve substantial risks and uncertainties. All statements included in this presentation, other than statements of historical facts, are forward-looking statements. Forward-looking statements include, without limitation, statements about the product candidates of Catalyst Biosciences, Inc. (the “Company”) and the benefits of its protease engineering platform, potential commercial opportunities for and advantages of MarzAA and DalcA, including their potential to treat hemophilia subcutaneously; plans to enroll the Crimson 1 Phase 3 registration study and report on actions of the DSMB and treatment of bleed data for this study; plans to enroll the MAA Phase 1/2 study of MarzAA and report PK and treatment of bleed data for this study; the potential markets for and advantages of the Company's complement product candidates, including CB 2782-PEG as a potential best-in-class C3 degrader for dry AMD, CB 4332 as a potential treatment for CFI deficiency, and complement degraders; plans for the Company's collaboration with Biogen; potential markets for the Company’s CFI complement product candidates, and plans to enroll the CB 4332 observational trial and to conduct human clinical trials for CB 4332. Actual results or events could differ materially from the plans, intentions, expectations and projections disclosed in the forward-looking statements. Various important factors could cause actual results or events to differ materially, including, but not limited to, the risk that trials, studies or programs may be delayed or terminated as a result of COVID-19 and other factors, that trials may not have satisfactory outcomes, that human trials will not replicate the results from earlier trials, that the Company will need to raise additional capital, which may not be available on favorable terms, if at all, the risk that costs required to develop or manufacture the Company’s products will be higher than anticipated, including as a result of delays in development and manufacturing resulting from COVID-19 and other factors, the risk that Biogen will terminate its agreement with the Company, competition and other risks described in the “Risk Factors” section of the Company’s Annual Report on Form 10-K filed with the Securities and Exchange Commission ("SEC") on March 4, 2021, on Form 10-Q filed with the SEC on August 5, 2021, and in other filings with the SEC. The forward-looking statements in this presentation represent the Company's view as of the date of this presentation and the Company does not assume any obligation to update any forward-looking statements, except as required by law. © Catalyst Biosciences
Novel differentiated medicines Robust complement portfolio Clinical-stage assets Unique expertise in protease engineering Harnessing the catalytic power of proteases The Protease Medicines Company © Catalyst Biosciences
Unique expertise enables design of optimized & differentiated protease candidates Catalyst protease platform Functionally enhanced natural proteases in the complement & coagulation cascades Engineered novel protein degraders in the complement cascade Modulate or target biological activation or inactivation Protease Scaffold Protease Candidate Our Proteases Discovery Platform Engineered Regulation Pharmacokinetic Improvement Structure Guided Design Molecular Evolution © Catalyst Biosciences
Requires high concentrations in excess of the target Requires high concentrations & frequent dosing Efficient regulation at low concentrations of therapeutic protease Proteases are ideal for high abundancy targets & cascades A better way to regulate biological processes compared with antibodies & small molecules Antibodies Small molecules / peptides Therapeutic target neutralization © Catalyst Biosciences Protease
R PC P1/2 P2 P3 Pipeline Hemostasis SQ Marzeptacog alfa (FVIIa) "MarzAA” Hemophilia A or B with inhibitors – ToB FVIID/Glanzmann/Hemlibra – ToB Complement IVT CB 2782-PEG C3 degrader for Dry AMD SQ CB 4332 Enhanced CFI (ConFIrm) C4b Degrader Additional programs Hemostasis SQ Dalcinonacog alfa (FIX) “DalcA” Hemophilia B CB 2679d-GT Hemophilia B FIX Gene Therapy © Catalyst Biosciences Observational Study
Validated across three programs Catalyst protease platform Before treatment On treatment Marzeptacog alfa (activated) Dalcinonacog alfa CB 2782-PEG Engineered rFVIIa protease 90% reduction in annualized bleed rate Achieved sustained & high target levels of FIX Best-in-class profile for dry AMD Extended pharmacodynamics Engineered rFIX protease Novel C3 degrader 50% 5% 1% Mild Hemophilia Normal clotting levels Severe Hemophilia Moderate Hemophilia © Catalyst Biosciences
Designed to address a clear unmet need in hemophilia & other bleeding disorders Marzeptacog alfa (activated) – MarzAA: SQ rFVIIa 9-fold higher activity vs NovoSeven RT Potency allows for SQ dosing that prolongs half-life NovoSeven RT is administered IV Preclinical efficacy of SQ episodic ToB HA mouse after tail cut; HA dog; HA rat P2 proof of concept & preliminary safety in HA or HB with inhibitors – prophylactic ToB 46 patients treated including: single dose IV, up to 3 SQ doses/day, & daily SQ up to 97 days – no ADA FDA Fast Track designations HA/HB with inhibitors, episodic ToB FVIID, episodic ToB P129A M298Q T128N Increased procoagulant activity Q286R © Catalyst Biosciences
SQ MarzAA is a large commercial opportunity Global NovoSeven sales breakdown by indication (2020) Hem A Inh (50.3%) Other (19.7%) Glanzmann (6.9%) Source: Adivo Associates market research; Catalyst Biosciences market research. Data on file. Hem B Inh (11.7%) FVII Def (4.9%) AHA (6.5%) SQ is patient-preferred & eliminates IV barrier to fast & effective treatment Ideal for pediatrics & patients with venous access issues Long half-life without high Cmax for optimal control of bleeds In vitro data support combination with Hemlibra® without increased thrombogenicity Prophylaxis opportunity demonstrated in P2 SQ MarzAA profile © Catalyst Biosciences
MarzAA could provide SQ prophylaxis for Glanzmann & FVIID Global NovoSeven on demand sales Glanzmann Thrombasthenia, FVIID Unmet need in prophylaxis Growing number of Glanzmann Thrombasthenia and FVIID patients treated with NovoSeven Source: Catalyst Biosciences, Adivo Associates Market Research, Data on file. *Note: 2019 estimates Treated patients may be counted multiple times as patients may have multiple bleeding events per year needing factor treatment 9% total increase in patients over 3 years © Catalyst Biosciences
Unmet need for a long-acting SQ episodic treatment of bleeds Source: 1NovoSeven PI Rev 7/2020; 2Adivo Associates market research; 3Catalyst Biosciences’ market research; Data on file; Neuman et al. ISTH 2020 Patients reported needing an average of 6 hours and 3 infusions of NovoSeven to resolve bleeds Some bleeds take longer than 72 hours to resolve1,2,3 NovoSeven Current bypass agents require multiple infusions over the course of hours MAA-102: PK MarzAA levels support SQ ToB Target therapeutic levels are rapidly achieved Target levels can be maintained for 18 hours with a single SQ dose of 60 μg/kg MarzAA Clinical MarzAA levels support SQ ToB © Catalyst Biosciences
Hemophilia A or B with inhibitors, ABR ≥ 8 Crimson 1 Phase 3 study: Treatment of episodic bleeding MarzAA SQ 60 µg/kg 1-3 doses 130 bleeds per sequence ≤5 bleeds per patient N = 30 SOC IV 1-3 doses ≤5 bleeds per patient 114 bleeds per sequence MarzAA SQ 60 µg/kg 1-3 doses ≤5 bleeds per patient 114 bleeds per sequence 130 bleeds per sequence ≤5 bleeds per patient SoC IV 1-3 doses N = 30 Primary endpoint Non-inferior hemostatic efficacy: standard 4-point scale at 24 h Secondary endpoints Time to bleed resolution; number of doses; rescue meds Safety Adverse events, anti-drug antibodies (ADA); thrombosis Statistics + SoC estimate 85% Excellent/good treatment of bleeds + Non-inferiority margin of 12% + 2.5% significance, one-sided + 90% power © Catalyst Biosciences
FVII deficiency, Glanzmann Thrombasthenia and HA on Hemlibra: N = 8 each MAA-202 Phase 1/2 study design Phase 1 Primary endpoint: Pharmacokinetics Secondary endpoint: Pharmacodynamics Phase 2 ToB Primary endpoint: Hemostatic efficacy at 24 hours Secondary endpoints: Effective hemostasis at successive timepoints; doses needed; rescue meds Safety: Adverse events and ADA Single dose Single dose escalation GT ≥30 bleeds FVIID ≥30 bleeds Phase 2 ToB Phase 1 PK MarzAA IV each cohort MarzAA SQ HA ≥15 bleeds MarzAA SQ 1-3 doses Multiple dose Q3H © Catalyst Biosciences
Growing Complement Pathway Protease Platform © Catalyst Biosciences
Complement is a perfect fit to develop protease therapeutics The complement pathway is driven by a protease cascade Source: Figure adapted from Mastellos et al., Clinical promise of next-generation complement therapeutics. Nature Reviews. 2019 of the complement cascade is regulated by proteases 80 % Exacerbation Immune modulation Immune modulation C1qR C3aR C1s C1r AAb NAb Neoepitopes/ autoepitopes Damaged/altered/foreign cells and debris C1-INH C2 C4 C4a C4b2b C3 Extrinsic protease C3a C3a-dR CPN C3b C4b2b3b C3bBb3b C5 convertase C5 C5b C5a Chemotaxis, inflammatory signaling and cell activation C5aR2 C5aR1 C5a-dR CPN MAC C6 C7 C8 C9n Extrinsic proteases CD59 MBL Fcn CL MASP1 MASP2 C1q Tick-over C3*Bb C3bBb pFD FP FP FD FB FH FP MASP3 C3* C3 C3b FP ? ? FB FD C3bBb C3 convertase FP FD FB FH CD55 CR1 C3b iC3b CD46 FH FI CR1 C3dg FI CR1 CR2 CR4 CR3 CR1 CR46 Exacerbation DAMP Amplification Immune modulation Adhesion Phagocytosis Trafficking Signaling Adaptive signaling Lysis, cell damage Terminal pathway Breakdown pathway CP LP AP Circulation turnover FI FI C4BP FI FH FI FI FH © Catalyst Biosciences
© Catalyst Biosciences Multiple, high-value complement programs CB 4332 C4b C3a CB 2782-PEG C3b C5a NextGen Degraders Future Degraders Development Candidate Novel Engineered Degrader Partnered with Biogen Established Catalyst Biosciences in complement Leads expansion into systemic complement in CFI dysregulation Specific & potent degraders target classical & alternative complement disorders with large-market potential Broadens Catalyst Biosciences footprint in the complement space
Unique targeted approach to complement regulation C3 C5 C3a C3b C5a Classical pathway Membrane attack complex (MAC) Immune response inflammation Lectin pathway Alternative pathway C4b MASP C4 C2 C1r C1s C3b C5b C3 (H2O) FD FB Cascade initiation Cascade regulation Terminal complement C4b Degraders C3b Degraders NextGen Degraders Other programs (CFx) CB 2782-PEG CB 4332 © Catalyst Biosciences
CB 2782-PEG: Best-in-class C3 degrader for dry AMD Protease advantage demonstrated in vivo CB 2782-PEG degrades C3 levels in the eye for at least 28 days in a non-human primate model Catalytic advantage of proteases One therapeutic molecule neutralizes 1000s Fast & potent response Extended pharmacodynamic effect Can activate or degrade therapeutic targets Engineered novel protein degraders “sweep away” difficult to drug targets CB 2782-PEG (nM) Days C3 Concentration (nM) © Catalyst Biosciences
© Catalyst Biosciences CB 2782-PEG: Long acting anti-C3 protease for dry AMD *Furfine et al. ARVO 2019 Geographic atrophy is a high unmet need Advanced stage of dry age-related macular degeneration (dAMD) dAMD affects ~1M people in the US & >5M WW, no currently approved therapy Global market ~ >$5B C3 is a clinically validated target (randomized P2) for dAMD Best-in-class C3 degrader for dry AMD Generated from Catalyst’s proprietary protease engineering platform Potent, selective & long acting, degrades C3 into inactive fragments NHP PK & PD data* predict best-in-class human intravitreal dosing 3 or 4 times a year Biogen collaboration $15M upfront, up to $340M in milestones & tiered royalties up to low double digits Catalyst: fully funded pre-clinical & manufacturing activities Biogen: IND-enabling activities, WW clinical development & commercialization
© Catalyst Biosciences CB 4332: SQ Enhanced Complement Factor I Development candidate to restore regulation 1Bienaime et al. Kidney Int. 2010; 2Ferreira et al. Nefrologia. 2016; Note: CFI = Complement factor I; Structural model based on PDB 2XRC. Engineered for an extended half-life Once weekly SQ therapy – no PEG In vitro & ex vivo activity comparable to native CFI Classical & alternative pathway regulation High yield production process Rebalance the complement system in patients with dysregulated CFI No specific therapies exist to correct CFI dysregulation Targets population with no treatment or who respond poorly to current treatments1,2 Rationale & unmet need
CB 4332: To address CFI deficiency at the root cause Designed to provide unique advantages Unmet needs in CFI deficiency CB 4332 Designed to address Blocks complement-initiated cell destruction in the circulation Directly addresses root cause of disease Addresses extravascular hemolysis Preserves normal immune functions, e.g. to fight off infections Convenient weekly SQ administration © Catalyst Biosciences
CB 4332 Phase 1/2 Trials Screening Screening & natural history of disease studies ConFIrm & ConFIdence: preparing for Phase 1/2 Identifies Target Population / Feeds ConFIdence Study / Discovers Undiagnosed Disease Prospective Clinical & Biomarkers Assessment of CFI-Deficiency Disease While on SoC Screening Identification of CFI-deficient patients & key investigators for CB 4332 trials Discover undiagnosed disease, create program awareness & inform on biomarkers CB 4332 Phase 1/2 Trials ConFIrm study ConFIdence study CB 4332 Phase 1/2 Trials © Catalyst Biosciences
CB 4332: Phase 1/2 - First in human study Extended treatment to assess proof of concept (N=up to 15) Study parts Multiple Ascending Doses (N=up to 9) Single Ascending Doses (N=up to 12) Study design Phase 1 open-label, single & multiple ascending SQ doses & extended duration proof of concept Population: CFI-deficient patients Proposed starting dose 0.5 mg/Kg Goals Safety & tolerability PK characterization Assessment of complement biomarkers (C3, FB, FBb, Bb/FB ratio, iC3b, C3d, C3dg, AP50/AH50) Establish a Recommended Dose Regimen within the CFI normal range © Catalyst Biosciences
Diseases with CFI mutations have tremendous potential aHUS C3G IC-MPGN Geographic atrophy CFI Deficiency Current development targets Potential targets Chronic inflammation Recurrent infections Autoimmune disorders aHUS C3G IC-MPGN US / EU5 market opportunity Market opportunity in CFI deficient populations $500M+ CFI Deficiency First indication 0 0 0 Specific systemic therapies in development for patients with dysregulated CFI Therapies addressing the root cause of disease Approved treatments for C3G, IC-MPGN, CFID © Catalyst Biosciences Bresin et al. JASN. 2013; Fremeaux-Bacchi et al. ASN. 2013; Rui-Ru et al. Jour Rare Dis Res. 2018; Servais et al. Kidney Int. 2012; Iatropoulous et al. Mol Immunol. 2016; Hou et al. Kidney Int. 2014; Alba-Domiguez et al. J rare Dis. 2012. El Sissy et al. Front. Immunol. 2019; Shields et al. Front Immunol. 2019; Naesens et al. Jour Allergy & Clin Immunol. 2020; Yan et al. Clin Epi 2020; Smith et al. Nature Reviews. 2019; Noris et al. Clin J Am Soc Nephrol. 2010; CBIO KOL interviews Note: aHUS = atypical Hemolytic Uremic Syndrome, C3G = Complement 3 Glomerulopathy, IC-MPGN = Immune-Complex Membranoproliferative Glomerulonephritis, CFID = Complement Factor I Deficiency
Our protease platforms are tailored to specific indications Tuning functionality to restore complement homeostasis & immunoregulation ImmunoTUNE™ C3a-C5a ProTUNE™ C3b-C4b Nephrology Hematology oncology Neurology Immunology Autoimmune © Catalyst Biosciences
C3b-C4b degraders significantly reduce inflammation in vivo Significantly decrease in inflammatory markers involved in IgA nephropathy Inflammatory markers in IgA nephropathy Reduction of IFNγ & TNF⍺ involved in kidney damage & proteinuria in IgA nephropathy patients1, 2 1. Yano, N. et al. Phenotypic Characterization of Cytokine Expression in Patients With IgA Nephropathy. J Clin Immunol 17, 396–402 (1997). 2. Lim, C. S. et al. Th1/Th2 predominance and proinflammatory cytokines determine the clinicopathological severity of IgA nephropathy. Nephrol Dial Transpl 16, 269–275 (2001). Values are mean +/- SEM, ***p<0.001 using One Way or Two-way ANOVA. Rat model of complement-mediated inflammation © Catalyst Biosciences
C3b-C4b degraders for IgA nephropathy patients Dual targeting of alternate & lectin pathways Classical pathway Lectin pathway C4 C2 C1r C1s MASPs C1q MBL C4b 2b C3 Alternative pathway CFB C3(H2O) CFD C3b Bb Differentiation Dual targeting mode of action: lectin & alternative pathways Rationale for IgA nephropathy Both lectin & alternative pathways are involved in IgA nephropathy & correlate with severe clinical manifestation 1, 2, 3 Clinically validated targets Inhibition of only MASP2 or Factor B may be insufficient to reduce proteinuria in IgA nephropathy patients Clinically validated target for IgAN 1. Medjeral-Thomas et al. Kidney International Reports (2018); 2. Bi et al. BMC Nephrology (2019); 3. Roos et al. J Am Soc Nephrol (2006) Clinically validated target for IgAN SPECIFICITY ProTUNE™ PLATFORM C4b C3b © Catalyst Biosciences
C3a-C5a degraders: Efficacy in an acute LPS-induced ARDS model CFx improves respiratory function & reduces cell infiltrates CFx 7-fold lower dose vs. anti-C5 Respiratory functions & cell infiltration at 24 h CFx outperforms anti-C5 antibody in reducing inflammatory cell infiltration CFx compares well on respiratory functions with anti-C5 antibody Mouse LPS model of lung inflammation CFx CFx © Catalyst Biosciences
C3a-C5a degraders: Potential for ANCA-AAV patients Dual targeting of both C3a & C5a with one protease medicine C3b C3 C5 C3a C5a C5b C3 convertase C3 convertase C3aR C5aR Clinically validated targets for ANCA Differentiation Degrade activation products of C3 (C3a) & C5 (C5a) that are inflammatory mediators May provide beneficial function via C5L2 pathway Rationale for ANCA-AAV Both C3a & C5a are higher in active AAV patients1, 2 Clinically validated targets Inhibition of C5a or C5aR may be insufficient to increase remission rates in ANCA-AAV patients Classical pathway Lectin pathway Alternative pathway ImmunoTUNE™ PLATFORM C3a C5a SPECIFICITY 1. S. Moiseev et al. British Society for Immunology, Clinical and Experimental Immunology (2020); 2. Gou et al. Kidney International (2012). © Catalyst Biosciences
CB 4332 spearheads a deep pipeline in complement IND & next development candidate in 2022 CFI-HSA Replacement Indication Platform Technology 2021 2022 C3b-C4b IgA Nephropathy Discovery C3a-C5a ANCA-AAV Discovery CB 4332 CFI Deficiency Natural History Screening & Natural History Study CB 4332 Partial Deficiency IC-MPGN/aHUS/C3G Phase I/II CB 4332 Non-Deficiency Expansion Indications Phase I/II Indication Selection Biomarker Data CB 4332 CFI Deficiency Preclinical Phase I IND Development Candidates for Each Program © Catalyst Biosciences
Degrader platform updates CB 4332 observational trial CB 2782-PEG 2022 MarzAA (FVIIa) CB 2782-PEG (dAMD) Systemic complement MAA-202 PK data MAA-304 first DSMB MAA-202 ToB data CB 2782-PEG CB 4332 P1/2 MAA-304 ToB data Degrader platform updates MAA-304 final DSMB Milestones 2021 © Catalyst Biosciences
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