UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

 

FORM 8-K

 

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): December 9, 2017

 

CATALYST BIOSCIENCES, INC.

(Exact name of registrant as specified in its charter)

 

 

(650) 266–8674

Registrant’s telephone number, including area code

 

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).

Emerging growth company ☒

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. ☒

 

 

 

 

 

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On December 9, 2017, Catalyst Biosciences, Inc. delivered a presentation at the 59th American Society of Hematology (ASH) Annual Meeting in Atlanta, GA. A copy of the presentation is attached hereto as Exhibit 99.1 and incorporated herein by reference.

The information in this Item 7.01 of this Current Report on Form 8-K (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. The information in this Current Report shall not be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such a filing.

 

 

On December 11, 2017, Catalyst Biosciences, Inc. issued a press release announcing interim Phase 1/2 data on its subcutaneously administered, prophylactic Factor IX variant CB 2679d/ISU304 that were presented at the 59th American Society of Hematology (ASH) Annual Meeting and Exposition in Atlanta, GA, on December 9, 2017.

 

A copy of the press release announcing the interim Phase 1/2 data is attached hereto as Exhibit 99.2 and is incorporated herein by reference.

(d) Exhibits.

 

 

 

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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.

 

 

 

Exhibit 99.1

 

Phase1/2 Trial of Subcutaneously Administered Factor IX Variant CB 2679d/ISU304: Pharmacokinetics and Activity Chur Woo You, MD PhD, Ho-Jin Shin, MD, Howard Levy MBBCh PhD, Martin Lee, PhD, Seung-Beom Hong, PhD, Jamie Ellen Siegel, MD and June Young Park, MD 87 Session 322. Disorders of Coagulation or Fibrinolysis: Novel Therapies and Clinical Trials in Bleeding Disorders ASH 9 December 2017

 

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Disclosure Employee and Stockholder of Catalyst Biosciences

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Factor IX Modified with 3 Point Mutations Rapid clearance of FIX necessitates frequent intravenous administrations to achieve effective prophylaxis Subcutaneous administration is the preferred route of administration but has been limited by low bioavailability and potency of the marketed FIX products Designed as best-in-class high potency recombinant FIX product Orphan Drug Designation in US and EU Factor IX: CB 2679d/ISU304

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CB 2679d/ISU304 Potency Advantage over wt-FIX 20-fold increased potency of CB 2679d over wild-type FIX in tail clip model

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Normalization of FIX Activity and Rapid Whole Blood Clotting Time Correction with Daily SQ Dosing of Cb 2679d/ISU304 (300 IU/kg) in Hemophilia B Dogs*

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Design of Ongoing Phase 1/2 Trial ISU Abxis is executing the Phase 1/2 trial Cohort 3 has been completed

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Methods IV PK was sampled at predose, 0, 0.25, 0.5, 1, 3, 6, 9, 24, 48 and 72 hours SQ PK was sampled at predose, 1, 2, 4, 6, 8, 10, 12, 24, 48 and 72 hours A safety follow-up was done 3 weeks after dosing FIX antigen and FIX activity, anti-drug antibody to BeneFIX and ISU304 and neutralizing antibody were measured at Haematologic Technologies FIX antigen was measured using VisuLize™ Factor IX Antigen KitAG (Affinity Biologicals) and FIX activity was measured using a one-stage clotting assay using ACL TOP 700 and Instrumentation Laboratories reagents Calculation of AUC was based on the trapezoidal rule Calculation of half-life used Demitasse 2000 which uses an iterative piecewise fitting algorithm based on a robust (M-regression) log-linear model All activity data were adjusted for baseline assuming exponential falloff after IV administration and a half-life of 20 hours

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Cohort 1, 2 & 3: IV BeneFIX & IV CB 2679d/ISU304 75 IU/kg

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IV BeneFIX vs IV CB 2769d/ISU304 PK 75 IU/kg PK profiles after IV administration (mean ± SD) Groupt-half alpha (hrs) t-half beta (hrs) MRT (hrs)Cmax(mU/mL)AUC 0-t (mU/mL hr)AUC 0-inf (mU/mL*hr)BeneFIX5.3 ±0.8 21.0 ± 1.1 25.1 ± 1.570.2 ± 16.0 855±163933±177 CB 2679d/ ISU3048.5 ±4.027.0 ±2.235.8 ±2.570.0 ±46.9973 ± 2741148 ±334P-value by two-sample0.220.00140.000040.9950.500.32 *ignoring the matching from Cohort 1t-test*

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Cohort 2: 75 IU/kg IV then 75 IU/kg SQ CB 2679d/ISU304 10

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Cohort 3: 75 IU/kg IV then 150 IU/kg SQ CB 2679d/ISU304

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CB 2769d - ISU304-001 PK:SQ vs IV has 3.6-fold Increase in Half-life Cohort 2 & 3: PK activity profiles after IV and SQ CB 2679d/ISU304 administration 98.7 hour SQ CB 2679d half-life is similar to IV agents dosed biweekly or weekly: Alprolix 86.52 hours Idelvion 104-118 hours Rebinyn/Refixia114.9 hours

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ISU-304-001 Safety One subject had a mild general reaction within 1 hour of injection Fatigue/Boredom Headache Dizziness Transient mild AEs were reported in cohorts 2 and 3 and all resolved without sequelae: Itching Tenderness Erythema Solidification Injection site discomfort General ache [moderate severity]

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Modeling of Daily 75 IU/kg SQ t1/2= 36 hoursModeling demonstrates that CB 2679dcouldachieve stable FIX minimum levels in the high mild hemophilia or normal range >50%

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Modeling of Daily 60 IU/kg SQ t1/2 = 100 hours Normal FIX activity levels of >50% are reached after 7 daily doses ofCB 2679d No difference between peak and minimum levels when Tmax is 24 hours Lower doses of CB 2679d will maintain levels above 50% at all times Less frequent dosing is also a possibility

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Modeling Predicts Subcutaneous Administration may be a Superior Prophylaxis Regimen Compared with IV Agents Time in Mild to Normal Levels Predicts Protection from Spontaneous Bleeds Illustrative Clotting Agent Activity Level Time after Dosing SQ Subcutaneous Drug Administration IV Drug Administration

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CB 2679d/ISU304 Program Conclusions CB 2679d is designed as best-in-class high potency recombinant Factor IX product 22-fold potency advantage allows subcutaneous administration Normal trough factor IX blood levels achieved after 6 daily subcutaneous doses in hemophilia B dogs Phase 1/2 subcutaneous trial is ongoing Cohort 3 (150 IU/kg SQ) has been completed Multi-dose SQ data anticipated Q1 2018 IV CB 2679d has a longer half-life of 27 hours than 21 hours of wt-FIX SQ delivery significantly increases half-life 3.6-fold to 98.7 hours SQ dosing may provide superior prophylaxis to IV extended half-life agents Orphan drug designations have been granted in US and EU

 

 

Exhibit 99.2

Catalyst Biosciences Announces Interim Phase 1/2 CB 2679d/ISU304 Results at the American Society of Hematology Conference

 

Subcutaneous (SQ) delivery significantly increases half-life of CB 2679d to 98.7 hours

 

Data supports potential normalization of FIX activity with daily or less-frequent SQ dosing

 

SOUTH SAN FRANCISCO, Calif., December 11, 2017 – Catalyst Biosciences, Inc. (NASDAQ: CBIO), a clinical-stage biopharmaceutical company focused on developing novel medicines to address hematology indications, today announced interim Phase 1/2 data on its subcutaneously administered, prophylactic Factor IX variant CB 2679d/ISU304 in an oral presentation at the 59th American Society of Hematology (ASH) Annual Meeting and Exposition held on Dec. 9-12, 2017 in Atlanta. The data demonstrate that subcutaneous delivery of CB 2679d significantly increases the factor IX (FIX) activity half-life to 98.7 hours.

 

Dr. Howard Levy, chief medical officer of Catalyst, presented results from the first three cohorts of the Phase 1/2 trial of CB 2679d in patients with severe hemophilia B. During these first three cohorts, patients received single intravenous (IV) and subcutaneous (SQ) doses of CB 2679d. Results from cohort 1, which compared 75 IU/kg IV CB 2679d with 75 IU/kg IV BeneFIX, showed that IV CB 2679d is approximately 22 times more potent and has a significantly longer half-life (27 vs 21 hours, p = 0.0014) and mean residence time than BeneFIX (36 hours vs 25 hours, p = 0.00004). Cohorts 2 and 3 compared 75 IU/kg IV CB 2679d with 75 IU/kg and 150 IU/kg SQ CB 2679d respectively. These results showed that SQ delivery of CB 2679d had a bioavailability of 18.5% and significantly increases the FIX activity half-life to 98.7 hours vs 27.6 hours for a IV dose of 75 IU/kg, (p = 0.005). No serious adverse events were observed. The data to date support the potential of achieving normal FIX levels in individuals with hemophilia B with daily or less frequent subcutaneous dosing.

 

“The results from these first three cohorts demonstrate the promise of CB 2679d as a safe prophylactic treatment for patients with hemophilia B,” said Dr. Levy. “The significantly increased half-life of CB 2679d and bioavailability after subcutaneous dosing suggests that CB 2679d may provide superior prophylaxis capabilities compared with intravenous extended half-life agents, with the potential to normalize FIX levels. We eagerly await the results from daily subcutaneous doses of CB 2679d on Factor IX blood levels that are expected in early 2018.”

 

About the Phase 1/2 Trial

CB 2679d is designed as a best-in-class high potency recombinant Factor IX product. The Phase 1/2 clinical trial of CB 2679d in patients with severe hemophilia B is being conducted at three centers in South Korea by the Company’s collaborator, ISU Abxis, which uses ISU304 as an alternate product name. The trial aims to measure the subcutaneous bioavailability and clotting ability of CB 2679d achieved after single intravenous and subcutaneous dosing in the first four cohorts, followed by daily subcutaneous injections of CB 2679d in the fifth, and final, cohort. In

 

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June 2017, the European Commission and in September 2017, the U.S. Food and Drug Administration (FDA) granted orphan drug designations for CB 2679d. Complete trial results are expected in early 2018.

 

About Catalyst

Catalyst is a clinical-stage biopharmaceutical company focused on developing novel medicines to address hematology indications. Catalyst is focused on the field of hemostasis, including the subcutaneous prophylaxis of hemophilia and facilitating surgery in individuals with hemophilia. For more information, please visit http://www.catalystbiosciences.com/.

 

Forward-Looking Statements

This press release contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statement of historical facts, included in this press release regarding our strategy, the potential uses and benefits of CB 2679d and development plans for this product candidate are forward-looking statements. Examples of such statements include, but are not limited to, statements relating to Catalyst’s clinical trial timelines, including the anticipated completion of a Phase 1/2 proof-of-concept study for CB 2679d, the plans to disclose complete trial results by early 2018, and the potential uses and benefits of subcutaneously dosed CB 2679d. Actual results or events could differ materially from the plans and expectations and projections disclosed in these forward-looking statements. Various important factors could cause actual results or events to differ materially from the forward-looking statements that Catalyst makes, including, but not limited to, the risk that trials and enrollment may be delayed and may not have satisfactory outcomes, that later trials will not replicate the results from earlier trials or preclinical studies, that potential adverse effects may arise from the testing or use of Catalyst’s products, including the generation of antibodies, the risk that costs required to develop or manufacture Catalyst’s products will be higher than anticipated, competition, and other factors described in the “Risk Factors” section of the Company’s most recent Quarterly Report on Form 10-Q filed with the SEC on November 2, 2017. Catalyst does not assume any obligation to update any forward-looking statements, except as required by law.

 

Contacts:

Investors:

Fletcher Payne, CFO

Catalyst Biosciences

1.650.871.0761  

investors@catbio.com

 

Media:

Josephine Belluardo, Ph.D.

LifeSci Public Relations

1.646.751.4361

jo@lifescipublicrelations.com