On November 6, 2023 Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT), a leading late-stage biotechnology company advancing an integrated and sustainable pipeline of genetic therapies for rare disorders with high unmet need, reported financial results for the quarter ending September 30, 2023, and updates from the Company’s key pipeline developments, business operations and upcoming milestones (Press release, Rocket Pharmaceuticals, NOV 6, 2023, View Source [SID1234637080]).

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"I’m very pleased with Rocket’s results this quarter, as we realized significant regulatory milestones across our pipeline, including reaching FDA alignment on the study design for the 10-patient Phase 2 pivotal trial of RP-L301 for the treatment of severe PKD and securing the FDA’s acceptance of Rocket’s BLA for RP-L201, now named KRESLADITM, for the treatment of severe LAD-I," said Gaurav Shah, M.D., Chief Executive Officer, Rocket Pharma. "At the same time, we initiated the Phase 2 pivotal trial of RP-A501 for Danon Disease following FDA alignment and the Phase 1 study of RP-A601 for PKP2-ACM, which move us substantially closer to delivering potential one-time, curative therapies to patients facing these two devastating cardiac diseases."

Dr. Shah continued, "As we bring 2023 to a close, we have made remarkable progress across the breadth of our AAV cardiovascular and LV hematology portfolios. Four programs have now reached pivotal studies, one of which is under review for approval, thanks to strong collaboration with health authorities and scientific partners, as we collectively seek to fulfill the high unmet needs of patients with rare and life-threatening diseases."

Key Pipeline and Operational Updates

AAV Cardiovascular Portfolio

Danon Disease

Initiated Phase 2 pivotal trial of RP-A501 for Danon Disease following FDA alignment. The global Phase 2 multi-center trial is a single arm study with an external comparator arm and includes 12 male patients with Danon Disease. The trial is evaluating the safety and efficacy of RP-A501 at a dose level of 6.7 x 1013 GC/kg and includes a pediatric safety run-in (n=2). The co-primary endpoint is composed of LAMP2 protein expression and left ventricular (LV) mass index and will be assessed at 12 months for accelerated approval.
Supported peer-reviewed expert consensus paper to increase awareness of diagnosis and clinical management of patients with Danon Disease. "International Consensus on Differential Diagnosis and Management of Patients with Danon Disease: JACC State-of-the-Art Review" was published in the Journal of the American College of Cardiology. Highlights of the publication include a review of diagnosing Danon Disease emphasizing the importance of genetic testing upon clinical suspicion, natural history, management recommendations and recent advances in potential gene therapy treatment.
Filed Clinical Trial Application (CTA)/Investigational Medicinal Product Dossier (IMPD) for RP-A501 to EMA and MHRA. Rocket is working towards initiation of Phase 2 pivotal trial activities in Europe and the UK.
PKP2 Arrhythmogenic Cardiomyopathy (PKP2-ACM)

Initiated Phase 1 trial of RP-A601. The multi-center Phase 1, dose escalation trial will evaluate the safety and preliminary efficacy of RP-A601 in at least six adult PKP2-ACM patients with ICDs and overall high risk for arrhythmias. The study will assess the impact of RP-A601 on PKP2 myocardial protein expression, cardiac biomarkers, and clinical predictors of life-threatening ventricular arrhythmias and sudden cardiac death. Patients in the dose-escalation trial will receive a single dose of RP-A601. The starting dose will be 8 x 1013 GC/kg.
LV Hematology Portfolio

Leukocyte Adhesion Deficiency-I (LAD-I)

BLA accepted by FDA with Priority Review for KRESLADITM (marnetegragene autotemcel). Based on the positive top-line efficacy and safety data from the global Phase 1/2 study, the FDA accepted the BLA and also granted Priority Review for KRESLADITM, also known as RP-L201. This represents Rocket’s first product filing and is a significant milestone for both the Company and patients whose only current available treatment option is bone marrow transplant, which has substantial morbidity and mortality, and may not be available in time. The PDUFA date set by the FDA is March 31, 2024.
Fanconi Anemia (FA)

Product filings for RP-L102 anticipated in the first half of 2024 in the U.S. and Europe. Rocket is finalizing the CMC package with the FDA.
Pyruvate Kinase Deficiency (PKD)

Reached agreement with FDA on study design of Phase 2 pivotal trial of RP-L301. Based on positive safety and efficacy data from the Phase 1 study, Rocket has aligned with the FDA on the pivotal study design to support accelerated approval and is initiating a 10-patient, single-arm Phase 2 pivotal trial with a primary endpoint of ≥1.5 point Hgb improvement at 12 months.
Presented positive updated clinical data from Phase 1 trial of RP-L301 at the ESGCT Annual Meeting. Updated data demonstrated sustained efficacy in both adult patients with up to 36 months follow-up. Hemoglobin improvement relative to pre-treatment baseline was observed in both patients in the pediatric cohort with up to six months of available follow-up. Results also indicated favorable safety profile for RP-L301 in all four patients treated in the Phase 1 study.
Operational Updates

Published peer-reviewed risk assessment demonstrating low incidence of busulfan-related secondary malignancies in pediatric transplant recipients. "Busulfan and Subsequent Malignancy: An Evidence-based Risk Assessment" was published in Pediatric Blood & Cancer. Busulfan is utilized as conditioning prior to gene therapy in nonmalignant hematologic and related disorders. Researchers conducted a literature-based assessment of busulfan and subsequent late effects, concluding the incidence of busulfan-related secondary malignancies has been less than 1% in pediatric transplant recipients, and that the incidence of secondary cancers in pediatric patients receiving single-agent busulfan in non-malignant settings is likely to be substantially lower than 1%.
Raised net proceeds of $188.9M through public offering. On September 15, 2023, the Company completed a public offering of approximately 9.5 million shares of our common stock at a public offering price of $16.00 per share and pre-funded warrants to purchase 3.1 million shares of common stock at a price of $15.99 per warrant. The gross proceeds to Rocket from the public offering were approximately $201.3 million, net of $12.4 million of offering costs, commissions, legal and other expenses for net proceeds from the offering of $188.9 million.
Upcoming Investor Conferences

Stifel Healthcare Conference 2023, November 15
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Third Quarter Financial Results

Cash position. Cash, cash equivalents and investments as of September 30, 2023, were $437.2 million.
R&D expenses. Research and development expenses were $46.8 million for the three months ended September 30, 2023, compared to $43.4 million for the three months ended September 30, 2022. The increase in R&D expenses was primarily driven by increases in compensation and benefits expenses of $4.5 million due to increased R&D headcount, clinical trial expenses of $7.4 million, license expenses of $2.2 million, and non-cash stock-based compensation of $1.6 million. Increases noted were offset by decreases in manufacturing and development costs of $9.0 million and cost of direct materials of $3.3 million.
G&A expenses. General and administrative expenses were $18.6 million for the three months ended September 30, 2023, compared to $15.1 million for the three months ended September 30, 2022. The increase in G&A expenses was primarily driven by increases in commercial preparation expenses which consists of commercial strategy, medical affairs, market development and pricing analysis of $2.5 million and non-cash stock compensation expense of $1.0 million, partially offset by reduction in acquisition related expenses of $1.3 million.
Net loss. Net loss was $61.9 million or $0.75 per share (basic and diluted) for the three months ended September 30, 2023, compared to $57.8 million or $0.87 per share (basic and diluted) for the three months ended September 30, 2022.
Shares outstanding. 90,146,602 shares of common stock were outstanding as of September 30, 2023.
Financial Guidance

Cash position. As of September 30, 2023, Rocket had cash, cash equivalents and investments of $437.2 million. Rocket expects such resources will be sufficient to fund its operations through 2025, including producing AAV cGMP batches at the Company’s Cranbury, N.J. R&D and manufacturing facility and continued development of its six clinical and/or preclinical programs.

On November 6, 2023 Gilead Sciences, Inc. (Nasdaq: GILD) and Arcus Biosciences, Inc. (NYSE: RCUS) reported that domvanalimab plus zimberelimab and chemotherapy showed encouraging overall response rate (ORR) and six-month progression-free survival (PFS) rate results in a preliminary analysis from Arm A1 of the EDGE-Gastric study (Press release, Gilead Sciences, NOV 6, 2023, View Source [SID1234637079]). This ongoing Phase 2, multi-arm, global study is evaluating the safety and efficacy of various combinations of the Fc-silent anti-TIGIT antibody domvanalimab plus the anti-PD-1 antibody zimberelimab and chemotherapy in patients with locally advanced unresectable or metastatic gastric, gastroesophageal junction or esophageal adenocarcinoma. These results will be presented tomorrow during the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Monthly Plenary Series, a virtual forum for presentation and discussion of the latest cancer research.

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"The preliminary data from the EDGE-Gastric study underscore the potential role of dual anti-TIGIT and anti-PD-1-containing regimen in the treatment of gastroesophageal cancer where front-line chemotherapy with anti-PD-1 blockade is currently the standard," said Yelena Y. Janjigian, M.D., Chief Attending Physician of the Gastrointestinal Medical Oncology Service, Memorial Sloan Kettering Cancer Center, and a principal investigator for the EDGE-Gastric study. "These early data are encouraging and indicate the potential for the anti-TIGIT, domvanalimab-based therapy to improve upon anti-PD-1 and chemotherapy in this setting, with a similar safety profile to anti-PD-1 and chemotherapy."

At data cutoff (September 4, 2023), 41 patients were enrolled and treated with a median follow-up of 8.1 months; 24 patients (59%) remained on study treatment at time of data cutoff. Median time on treatment was 33 weeks (range: <1 to 53 weeks).

The domvanalimab-containing regimen showed an objective response rate (ORR) of 80% in patients with PD-L1-high tumors (tumor activity positivity (TAP) ≥5%), 46% in patients with PD-L1-low tumors (TAP <5%) and 59% for patients overall. There were two confirmed complete responses. Six-month landmark PFS rate was 93% for patients with PD-L1-high tumors (TAP ≥5%), 68% for patients with PD-L1-low tumors (TAP <5%) and 77% for patients overall. Median PFS was not reached and mature PFS data are expected in the second half of next year.

The efficacy results including ORR and six-month PFS rates are summarized in the table below:

PD-L1-high*

(TAP ≥5%)

N=15

n (%)

PD-L1-low* (TAP <5%)

N=24

n (%)

Overall

N=41

n (%)

ORR (95% CI)

80%

(52,96)

46%

(26,67)

59%

(42,74)

Confirmed ORR (95% CI)

73%

(45,92)

46%

(26,67)

56%

(40,72)

6-month PFS Rate (95% CI)

93%

(81,100)

68%

(48,88)

77%

(64,90)

*Tumor samples from 2 patients were not available for central PD-L1 testing

CI: confidence interval

The domvanalimab-containing regimen was well tolerated, with a similar safety profile to what has been reported for anti-PD-1 plus chemotherapy in this setting. The most common adverse events (AEs) were neutropenia (59%), nausea (54%), anemia (27%) and fatigue (27%). Infusion-related reactions were observed in 20% and the majority (17%) were related to chemotherapy. No patients experienced serious immune-mediated AEs, and there were no treatment-emergent adverse events (TEAEs) resulting in death.

These data add to the growing body of evidence that domvanalimab, an Fc-silent anti-TIGIT antibody, has a differentiated safety and tolerability profile relative to published data from studies with Fc-enabled anti-TIGIT antibodies.

The preliminary data from Arm A1 of the Phase 2 EDGE-Gastric study support the ongoing Phase 3 study, STAR-221, in unresectable or metastatic upper GI cancers. The companies have three additional ongoing Phase 3 registrational studies of domvanalimab-containing regimens in lung cancer, including STAR-121, ARC-10 and PACIFIC-8.

Domvanalimab and zimberelimab are investigational molecules. Neither Gilead nor Arcus has received approval from any regulatory authority for any use globally, and their safety and efficacy for the treatment of gastrointestinal and lung cancers have not been established.

About the EDGE-Gastric Study

The ongoing, multi-arm, global EDGE-Gastric trial (NCT05329766) is evaluating the safety and efficacy of various combinations of the Fc-silent anti-TIGIT antibody domvanalimab and the anti-PD-1 antibody zimberelimab in patients with locally advanced unresectable or metastatic gastric (G), gastroesophageal junction (GEJ) or esophageal (E) adenocarcinoma. Patients in Arm A1, with previously untreated G/GEJ/E adenocarcinoma, received 1600 mg of domvanalimab intravenously (IV) every four weeks (Q4w) plus 480 mg of zimberelimab IV Q4W + FOLFOX (oxaliplatin 85 mg/m2 IV, leucovorin 400 mg/m2 IV, fluorouracil 400 mg/m2 IV bolus + 2400 mg/m2 continuous 46-48-hour IV infusion) every two weeks.

About Domvanalimab

Domvanalimab is the first Fc-silent investigational monoclonal antibody in pivotal trials that is designed to block and bind to the T-cell immunoreceptor with Ig and ITIM domains (TIGIT), a protein receptor on immune cells that acts as a brake on the immune response. Cancer cells can exploit TIGIT to avoid detection by the immune system. By binding to TIGIT, domvanalimab is expected to free up immune activating pathways and activate immune cells to attack and kill cancer cells. Domvanalimab has demonstrated complete receptor coverage on all TIGIT-expressing peripheral leukocytes.

Domvanalimab is being evaluated in four registrational Phase 3 studies across lung and gastrointestinal cancers, including: (1) ARC-10, evaluating domvanalimab plus zimberelimab versus pembrolizumab in first-line locally advanced or metastatic PD-L1 ≥50% NSCLC; (2) PACIFIC-8, being operationalized by AstraZeneca, evaluating domvanalimab plus durvalumab in unresectable Stage 3 NSCLC; (3) STAR-121, evaluating domvanalimab plus zimberelimab and chemotherapy versus pembrolizumab plus chemotherapy in first-line PD-L1-unselected NSCLC; and (4) STAR-221, evaluating domvanalimab plus zimberelimab and chemotherapy versus nivolumab plus chemotherapy in first-line locally advanced, unresectable or metastatic gastric, esophageal and gastro-esophageal junction adenocarcinomas.

On November 6, 2023 Aura Biosciences, Inc. ("Aura") (Nasdaq: AURA), a clinical-stage biotechnology company developing a novel class of virus-like drug conjugate (VDC) therapies for multiple oncology indications, reported the pricing of an underwritten public offering of 11,000,000 shares of its common stock at a price to the public of $9.00 per share (Press release, Aura Biosciences, NOV 6, 2023, View Source [SID1234637078]). The gross proceeds from the offering to Aura are expected to be $99.0 million, before deducting underwriting discounts and commissions and other offering expenses. The offering is expected to close on or about November 9, 2023, subject to customary closing conditions. In addition, Aura has granted the underwriters a 30-day option to purchase up to 1,650,000 additional shares of common stock at the public offering price, less the underwriting discount.

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Leerink Partners, TD Cowen and Evercore ISI are acting as joint bookrunning managers for the offering. JMP Securities, A Citizens Company, is acting as lead manager for the offering.

A shelf registration statement relating to the shares of common stock offered in the public offering described above was filed with the Securities and Exchange Commission (the "SEC") on November 1, 2022 and declared effective by the SEC on November 7, 2022. The offering is being made only by means of a written prospectus and prospectus supplement that form a part of the registration statement. A preliminary prospectus supplement and accompanying prospectus relating to the offering has been filed with the SEC and is available on the SEC’s website at www.sec.gov. A final prospectus supplement and accompanying prospectus will be filed with the SEC. When available, copies of the final prospectus supplement and the accompanying prospectus may also be obtained by contacting Leerink Partners LLC, Attention: Syndicate Department, 53 State Street, 40th Floor, Boston, MA 02109, by telephone at (800) 808-7525, ext. 6105, or by email at [email protected]; Cowen and Company, LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, Attn: Prospectus Department, by telephone at (833) 297-2926, or by email at [email protected]; or Evercore Group L.L.C., Attention: Equity Capital Markets, 55 East 52nd Street, 35th Floor, New York, New York 10055; by telephone at (888) 474-0200, or by email at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy the securities being offered, nor shall there be any sale of the securities being offered in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.

On November 6, 2023 BerGenBio ASA (OSE: BGBIO), a clinical-stage biopharmaceutical company developing novel, selective AXL kinase inhibitors for severe unmet medical needs, reported that a poster presentation detailing additional data from a Phase II trial of bemcentinib in combination with MSD’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab) in second line Non-Small Cell Lung Cancer (NSCLC) patients was presented on November 4th at the 2023 Society of Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting (Press release, BerGenBio, NOV 6, 2023, View Source [SID1234637077]).

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The pre-planned biomarker analysis of the BGBC008 study in 2L NSCLC patients adds to the clinical data recently announced at the 2023 ESMO (Free ESMO Whitepaper) meeting. The poster presentation entitled "Bemcentinib + Pembrolizumab show promising efficacy in metastatic NSCLC patients harboring mutations associated with poor prognosis: exploratory sub-analysis from the BGBC008 Trial", is now available on BerGenBio’s website under the Scientific Publications section.

Martin Olin, Chief Executive Officer of BerGenBio, commented "The findings add to the industry’s understanding of the outcomes in 2L NSCLC patients and the potential for bemcentinib to benefit patients in combination with immune checkpoint inhibition. While the dataset in the analyses is relatively small, we believe bemcentinib in combination with pembrolizumab has the potential to improve outcomes in NSCLC patient sub-groups that have been associated with poor survival, including patients with negative/low PD-L1 levels, STK11 mutations, and KEAP1 mutations".

On November 6, 2023 Cellenkos Inc., a clinical stage biotechnology company focused on developing allogeneic, off-the-shelf, T regulatory (Treg) cell therapies for treatment of rare inflammatory diseases and autoimmune disorders, reported an oral presentation and poster presentation at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition, which is being held December 9-12, 2023, in San Diego, California (Press release, Cellenkos, NOV 6, 2023, View Source;exposition-301978056.html [SID1234637076]).

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The oral presentation will describe the differentiation and characterization of the CXCR4 enriched Treg cells and their preferential homing to bone marrow to resolve inflammation and decrease TGFβ1 and TGFβ2, in vivo, when compared to control Treg cells. This presentation has also been selected for ASH (Free ASH Whitepaper) Abstract Achievement Award.

The poster presentation will elaborate on the results of Company’s CK0804 Phase 1b trial. The study provides first-in-human safety of multiple infusions of CK0804 in myelofibrosis patients in the ambulatory setting as well as improvement in their blood transfusion requirements and symptom burden.

"We are very pleased with the breadth of our oral and poster presentations at this year’s ASH (Free ASH Whitepaper) meeting, which reflect the promising potential of CK0804 as the backbone for treating myelofibrosis," stated Tara Sadeghi, Chief Operating Officer of Cellenkos Inc. "Of particular note is the convergence of our CK0804 clinical data with the strong pre-clinical hypothesis and its mechanism of action. This marks dawn of a new era of differentiated Treg cell therapy that could be tailored to specific target tissue and can be investigated in combination with existing approved therapies, especially if there are complimentary mechanisms of action and favorable side effect profiles. The ability to administer CK0804 cells in ambulatory setting without requiring lymphodepletion or hospital admission, embarks the democratization of cellular therapies such that these potentially lifesaving treatments could be made available to patients in the community setting. In addition, the improvement in blood transfusions burden allows for CK0804 to be positioned as a potential novel therapy. We look forward to examining CK0804 in a larger trial."

Further details of the presentations are provided below.

Oral Presentation

Title: CXCR4 Enriched T Regulatory Cells Preferentially Home to Bone Marrow and Decrease Inflammation
Date: Saturday, December 9, 2023.
Time: 4:30 PM
Location: San Diego Convention Center, Room 6A

This oral presentation describes the CXCR4 enrichment of Treg cells using the CRANE technology platform and faster migration of CXCR4 enriched cells towards SDF1a as early as 15-minute time point. In vivo, the CXCR4 enriched Tregs preferentially trafficked to bone marrow and exhibit higher expression of CXCL12, CD62L, CD39, CD73 and CXCR5. A decrease in TGFα, TNFβ, IL-13 as well as TGFβ1 and TGFβ2 was also observed. These CXCR4 enriched Treg cells are being examined in phase 1b clinical trial (NCT05423691).

Poster presentation

Title: A Phase Ib, Open-Label Study of Add on Therapy with CK0804 in Participants with Myelofibrosis and Suboptimal Response to Ruxolitinib Date: Saturday, December 9, 2023
Time: 5:30 PM
Location: San Diego Convention Center, Halls G-H

This presentation describes the safety and efficacy data from the ongoing phase 1b LIMBER-TREG108 study evaluating CK0804, CXCR4 enriched, T regulatory cells, as an add on therapy to ruxolitinib in patients with myelofibrosis who experience a suboptimal response to ruxolitinib. This is a single arm study where patients receive 6 infusions of CK0804 at a fixed dose at 100 million Treg cells every 28 days. Clinical data from 5 patients who have completed treatment show early promising results of improvement in blood transfusion as well as relief from symptom burden. Additionally, patients report improvement in their tolerance of anemia and daily activities of life.