On February 16, 2024 Hepion Pharmaceuticals, Inc. (NASDAQ:HEPA), a clinical stage biopharmaceutical company focused on artificial intelligence assisted therapeutic drug development for the treatment of non-alcoholic steatohepatitis ("NASH"), fibrotic diseases, hepatocellular carcinoma ("HCC"), and other chronic diseases, reported that it has entered into a definitive agreement for the immediate exercise of an outstanding Series B common stock purchase warrant held by an institutional investor to purchase an aggregate of 980,393 shares of Hepion common stock for gross proceeds to the Company of approximately $2.0 million (Press release, Hepion Pharmaceuticals, FEB 16, 2024, View Source [SID1234640186]).

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As part of this transaction, the investor agreed to exercise the existing Series B common stock purchase warrant (which was originally issued in October 2023 and had an exercise price of $4.85 per share) at a revised exercise price of $2.10 per share. The resale of the shares of common stock issuable upon exercise of the warrant were registered pursuant to an effective registration statement on Form S-1 (No. 333-275231).

In consideration for the immediate exercise of the existing warrant for cash, Hepion has agreed to issue to the investor two new unregistered warrants, each to purchase 735,295 shares of common stock (or an aggregate of 1,470,590 shares) at an exercise price of $1.91 per share. The new warrants will be exercisable immediately upon issuance. Such warrants are identical, except that one warrant has a term of five years and the second warrant has a term of eighteen months.

A.G.P./Alliance Global Partners is acting as the exclusive financial advisor in connection with the offering.

The transaction is expected to close no later than February 21, 2024, subject to satisfaction of customary closing conditions. Hepion intends to use the net proceeds from the exercise for general corporate purposes.

The new warrants described above were offered in a private placement pursuant to an applicable exemption from the registration requirements of the Securities Act of 1933, as amended (the "Securities Act"), and, along with the shares of common stock issuable upon their exercise, have not been registered under the Securities Act or applicable state securities laws, and may not be offered or sold in the United States except pursuant to an effective registration statement or an applicable exemption from the registration requirements of the Securities Act and such applicable state securities laws. The Company has agreed to file a registration statement with the Securities and Exchange Commission (the "SEC") covering the resale of the shares of common stock issuable upon exercise of the new warrants.

In connection with the offering, the Company agreed to amend, effective upon the closing of this offering, the terms of the October 2023 Series A common stock purchase warrant held by a purchaser in the offering to reduce the exercise price thereof to $1.91 per share and to extend the expiration date to February 2029. All of the other terms of the October 2023 Series A common stock purchase warrant will remain unchanged.

This press release shall not constitute an offer to sell or a solicitation of an offer to buy these securities, nor shall there be any sale of these securities 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 February 16, 2024 Fusion Pharmaceuticals Inc. (Nasdaq: FUSN), a clinical-stage oncology company focused on developing next-generation radiopharmaceuticals as precision medicines, reported that it has entered into an exclusive worldwide license agreement with Heidelberg University and Euratom represented by the European Commission, Joint Research Centre (together, the "Licensors") (Press release, Fusion Pharmaceuticals, FEB 16, 2024, View Source [SID1234640185]). The license agreement grants Fusion exclusive worldwide rights to utilize, develop, manufacture and commercialize compounds covered by the patent, which includes 225Ac-PSMA I&T ("FPI-2265") for the treatment of prostate specific membrane antigen (PSMA)-expressing cancers. In addition, Fusion and the Licensors have signed an agreement to settle the parties’ dispute related to an inter partes review ("IPR") of a U.S. patent owned by the Licensors which was instituted in August 2023 by the United States Patent and Trademark Board.

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Fusion President and Chief Business Officer Mohit Rawat said, "We are pleased to enter into this exclusive license agreement with Heidelberg University and Euratom for their existing patent as we progress FPI-2265, the most advanced actinium-based PSMA targeted radiotherapy currently in development. With Fusion’s expertise in the development and manufacturing of alpha-emitting radiopharmaceuticals, an operational radiopharmaceutical manufacturing facility, and our advantageous actinium supply, we are well positioned to execute this program. We look forward to providing updates as we reach anticipated upcoming milestones in 2024, including data from the TATCIST study in April and the initiation of our Phase 2/3 registrational study in the second quarter."

As announced in January 2024, Fusion and the U.S. Food and Drug Administration reached alignment on Fusion’s Phase 2/3 protocol for FPI-2265 in patients with mCRPC who have progressed following treatment with lutetium-based radiopharmaceuticals. The updated development plan includes a Phase 2 dose optimization lead-in, expected to complete enrollment by the end of 2024, and a Phase 3 registrational trial expected to begin in 2025.

Under the terms of the license agreement, Fusion will pay the Licensors an aggregate upfront fee of €1.0 million, in addition to certain regulatory milestones upon potential approval and low single-digit royalties on future net sales of applicable products.

On February 16, 2024 BioLineRx Ltd. (NASDAQ/TASE: BLRX), a commercial stage biopharmaceutical company pursuing life-changing therapies in oncology and rare diseases, reported that new post-hoc subgroup analyses and pharmacodynamic data will be presented on APHEXDA (motixafortide) for CD34+ hematopoietic stem cell (HSC) mobilization in patients with multiple myeloma at the 2024 Tandem Meetings: Transplantation & Cellular Therapy Meetings of the American Society for Transplantation and Cellular Therapy (ASTCT) and the Center for International Blood and Marrow Transplant Research (CIBMTR), taking place February 21-24, 2024, in San Antonio, Texas (Press release, BioLineRx, FEB 16, 2024, View Source [SID1234640184]).

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Results include pharmacokinetics (PK) and pharmacodynamics (PD) data as well as post-hoc subgroup analyses from the Phase 3 GENESIS trial, a randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of APHEXDA (motixafortide) plus filgrastim, compared to placebo plus filgrastim (G-CSF), for the mobilization of hematopoietic stem cells for autologous transplantation in multiple myeloma patients. Phase 1 study results demonstrated an extended PD effect with complete receptor occupancy by motixafortide starting at a concentration of 3nM. In the GENESIS trial, post-hoc subgroup analyses based on baseline characteristics and risk factors for impaired HSC mobilization demonstrated a consistent benefit of motixafortide + G-CSF over placebo + G-CSF mobilization for all patients.

Poster Presentations at the 2024 Tandem Meetings: Transplantation & Cellular Therapy Meetings of the ASTCT and the CIBMTR.

Henry B. González Convention Center, San Antonio, Texas

Poster Session Details

Poster: Number 537. See abstract.
Title: Motixafortide Enables Consistent, Robust Hematopoietic Stem Cell Collection (HSC) across Populations with Increased Impaired HSC Mobilization: A Sub-Group Analysis of the Genesis Study

Presenter: Zachary D. Crees, MD, Washington University School of Medicine in St. Louis

Poster Session: Myeloma – Clinical

Date: Thursday, February 22, 2024

Time: 6:45 PM – 7:45 PM

Poster: Number 535. See abstract.
Title: Prolonged CXCR4 Receptor Occupancy By Motixafortide Following a Single Subcutaneous Injection Is Associated with Extended Mobilization of CD34+ Cells in Peripheral Blood for > 24 Hours

Presenter: Ella Sorani, PhD, BioLineRx Ltd

Poster Session: Myeloma – Clinical

Date: Thursday, February 22, 2024

Time: 6:45 PM – 7:45 PM

About the GENESIS Trial
GENESIS (NCT 03246529) is a 2-part, Phase-3, randomized, double-blind, placebo-controlled, multicenter study evaluating the safety and efficacy of APHEXDA (motixafortide) plus filgrastim (G-CSF), compared to placebo plus filgrastim, for the mobilization of hematopoietic stem cells for autologous transplantation in multiple myeloma patients. Part 1 was a single center, lead-in, open-label study involving 12 patients treated with motixafortide plus filgrastim designed to ascertain the dose. Part 2 involved 122 patients who were randomized 2:1 in a double-blind, placebo-controlled, multicenter study. The primary objective of the study was to evaluate if one dose of motixafortide plus filgrastim is superior to placebo plus filgrastim in the ability to mobilize ≥ 6 million CD34+ cells in up to two apheresis sessions. A key secondary objective of the study was to evaluate if one dose of motixafortide plus filgrastim is superior to placebo plus filgrastim in the ability to mobilize ≥ 6 million CD34+ cells in one apheresis session.

About Multiple Myeloma Multiple myeloma is an incurable blood cancer that affects some white blood cells called plasma cells, which are found in the bone marrow. When damaged, these plasma cells rapidly spread and replace normal cells in the bone marrow. According to the American Cancer Society, in 2024, it is estimated that more than 35,000 people will be diagnosed with multiple myeloma, and nearly 13,000 people will die from the disease in the U.S.1 While some people diagnosed with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, kidney problems, or infections.

About APHEXDA APHEXDA (motixafortide) is a CXCR4 antagonist with long receptor occupancy (greater than 72 hours) that, in combination with filgrastim (G-CSF), enables mobilization of hematopoietic stem cells to the peripheral blood for collection and subsequent autologous stem cell transplantation in patients with multiple myeloma.2

INDICATION AND IMPORTANT SAFETY INFORMATION

INDICATION
APHEXDA is indicated in combination with filgrastim (G-CSF) to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with multiple myeloma.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS
APHEXDA is contraindicated in patients with a history of serious hypersensitivity reactions to motixafortide.

WARNINGS AND PRECAUTIONS

Anaphylactic Shock and Hypersensitivity Reactions: Anaphylactic shock and hypersensitivity reactions have occurred. Premedicate all patients with a triple drug premedication regimen that includes an H1-antihistamine, an H2 blocker, and a leukotriene inhibitor approximately 30-60 minutes prior to each dose of APHEXDA. Administer APHEXDA in a setting where personnel and therapies are immediately available for treatment of anaphylaxis and other systemic reactions. Monitor patients for 1 hour following APHEXDA administration and manage reactions promptly. Patients receiving negative chronotropic drugs (e.g., beta-blockers) may be more at risk for hypotension in the event of a hypersensitivity reaction and these drugs, when appropriate, should be replaced with non-chronotropic drugs.
Injection Site Reactions: Injection site reactions (73%) including pain (53%), erythema (27%), and pruritus (24%) have occurred. Severe reactions occurred in 9% of patients. Premedicate with an analgesic premedication (e.g., acetaminophen) prior to each APHEXDA dose. Use analgesic medication and local treatments post-dose, as needed.
Tumor Cell Mobilization in Patients with Leukemia: For the purpose of hematopoietic stem cell (HSC) mobilization, APHEXDA may cause mobilization of leukemic cells and subsequent contamination of the apheresis product. Therefore, APHEXDA is not intended for HSC mobilization and harvest in patients with leukemia.
Leukocytosis: Administering APHEXDA in conjunction with filgrastim increases circulating leukocytes as well as HSC populations. Monitor white blood cell counts during APHEXDA use.
Potential for Tumor Cell Mobilization: When APHEXDA is used in combination with filgrastim for HSC mobilization, tumor cells may be released from the marrow and subsequently collected in the leukapheresis product. The effect of potential reinfusion of tumor cells has not been well-studied.
Embryo-fetal Toxicity: Based on its mechanism of action, APHEXDA can cause fetal harm. Advise pregnant women of the potential risk to the fetus. Verify pregnancy status in females of reproductive potential prior to initiating treatment with APHEXDA and advise use of effective contraception during treatment and for 8 days after the final dose.
ADVERSE REACTIONS
The most common adverse reactions (incidence >20%) in patients treated with APHEXDA were injection site reactions [73%, including pain (53%), erythema (27%), pruritus (24%)]; pruritus (38%); flushing (33%); back pain (21%).

USE IN SPECIFIC POPULATIONS

Pregnancy: Please see the important information in Warnings and Precautions under Embryo-fetal Toxicity.

Lactation: There are no data on the presence of motixafortide in human milk, the effects on the breastfed child, or the effects on milk production. Advise females that breastfeeding is not recommended during treatment with APHEXDA and for 8 days after the final dose.

Pediatric Use: The safety and effectiveness of APHEXDA have not been established in pediatric patients.

Please see the accompanying full Prescribing Information.

On February 15, 2024 Gilead Sciences, Inc. reported that it has paused enrollment globally in the magrolimab solid tumor studies. The U.S. Food and Drug Administration (FDA) subsequently requested a partial clinical hold on these trials (Press release, Gilead Sciences, FEB 15, 2024, View Source [SID1234640174]). This request is in addition to the previously announced full clinical hold on all magrolimab studies in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) requested by the FDA. Gilead is reviewing the benefit-risk of magrolimab across all ongoing trials and will provide an update on this assessment as soon as possible.

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Patients already enrolled in the Gilead-sponsored ELEVATE solid tumor studies and deriving clinical benefit may continue to choose receiving magrolimab following reconsenting to the study with their healthcare provider.

The Gilead-sponsored ELEVATE solid tumor studies impacted by the partial clinical hold include:

Phase 2 study in head and neck squamous cell carcinoma (NCT04854499)
Phase 2 study in solid tumors (NCT04827576)
Phase 2 study in triple-negative breast cancer (NCT04958785)
Phase 2 study in colorectal cancer (NCT05330429)
The enrollment hold also applies to Investigator Sponsored Studies with magrolimab in solid tumors.

On February 15, 2024 Firefly Bio reported that the company emerged from stealth mode with a $94 million Series A financing co-led by founding investor Versant Ventures and by MPM BioImpact alongside Decheng Capital and with participation from Eli Lilly & Company (Press release, Firefly Bio, FEB 15, 2024, View Source [SID1234640173]). Firefly has developed a novel platform to treat cancer using degrader antibody conjugates (DACs).

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DACs represent the convergence of two technologies – antibody drug conjugates (ADCs) and protein degraders. Despite the power of each approach, both have important limitations. While traditional ADCs have favorable bioavailability and the ability to target cells, they often have a limited therapeutic index due to their broadly cytotoxic payloads. Additionally, ADCs lack the ability to knock down specific intracellular proteins.

With protein degraders, the converse is true – these therapies have intracellular selectivity, protein knock down, and are highly catalytic. However, they struggle with bioavailability and do not have the ability for cell-specific targeting.

Firefly’s platform combines the respective strengths of ADCs and degraders while overcoming their deficiencies. The result is a new class of therapeutics able to precisely drug a range of intracellular biological targets that were previously hampered by therapeutic index issues when delivered systemically.

"DACs are a new modality for cancer," said Firefly CEO Scott Hirsch. "They give us the ability to hit biologically validated targets with minimal collateral damage. Our platform enables DACs at scale and vastly expands the number of payloads for ADCs."

An Industry-Leading Platform
Firefly’s platform uses potent catalytic protein degraders as the payloads of ADCs. The company’s proprietary Firelink linker technology joins these modalities, decreasing free payload in circulation and minimizing uptake in healthy cells. This leads to lower doses needed for optimal efficacy. In preclinical studies in both solid and liquid tumors, single administration of Firefly’s DACs showed significant reductions in tumor volume at very low doses.

Firefly was incubated in close collaboration with scientists at Versant’s Ridgeline Discovery Engine in the Basel Technology Park. These efforts helped the company rapidly establish proof-of-concept and advance its lead asset.

"At Firefly, we’ve assembled a unique talent base and platform to significantly advance this promising field," said Jerel Davis, Ph.D., Managing Director at Versant and a Firefly board member. "The company has made rapid progress and is poised to become the leader in discovering clinically meaningful DACs in oncology and immunology."

"Firefly is the first company with a platform specifically suited for DACs," said Todd Foley, managing director at MPM BioImpact and a Firefly board member. "The company’s platform upgrades multiple aspects of existing linker technologies and does so all under one roof, making it ideally positioned to pioneer these new therapies."

Leadership Team and Founders

Firefly is led by experienced executives with a deep history and expertise in biotech creation, ADC development, and degrader chemistry. The team is led by CEO, Scott Hirsch who was previously Chief Operating Officer at Allakos and has overseen multiple early- and late-stage ADC programs as well as directly managed commercial, portfolio, and operations teams. Co-founder and CSO John Flygare, Ph.D., previously led ADC teams at Genentech and Merck and has advanced ADCs and degraders into the clinic. Co-founder and CTO Bernhard Geierstanger, Ph.D., is a biotherapeutics expert and previously led ADC teams at Novartis and Merck and built protein modification and conjugation platforms. Co-founder Carolyn Bertozzi, Ph.D., was awarded the 2022 Nobel Prize in Chemistry for her work in bioorthogonal chemistry and is a world expert in ADCs.