On June 13, 2024 Syros Pharmaceuticals (NASDAQ:SYRS), a biopharmaceutical company committed to advancing new standards of care for the frontline treatment of hematologic malignancies, reported that it will host a webcast event with medical experts to discuss the unmet need in higher-risk myelodysplastic syndrome (HR-MDS) and the opportunity for tamibarotene to transform the care of newly diagnosed patients with RARA gene overexpression (Press release, Syros Pharmaceuticals, JUN 13, 2024, View Source [SID1234644308]). The event will take place on Tuesday, June 25, 2024, from 11:00 a.m. – 12:30 p.m. ET.

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Syros is currently evaluating tamibarotene in SELECT-MDS-1, a pivotal Phase 3 clinical trial in HR-MDS patients with RARA overexpression, and in SELECT-AML-1, a Phase 2 clinical trial in unfit acute myeloid leukemia (AML) patients with RARA overexpression. Syros expects to report pivotal complete response data from the SELECT-MDS-1 trial by the middle of the fourth quarter of 2024 and will report clinical activity and tolerability data from a prespecified analysis of over 40 patients from the SELECT-AML-1 trial in the third quarter of 2024.

The webcast event will feature presentations from Amy DeZern, M.D., M.H.S., Professor of Oncology and Medicine, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine, Amer Zeidan, M.B.B.S., M.H.S., Chief, Hematologic Malignancies, Yale Cancer Center and Smilow Cancer Hospital; Associate Professor of Medicine (Hematology), Yale School of Medicine and David Sallman, M.D., Myeloid Section Head and Associate Member, Department of Malignant Hematology, H. Lee Moffitt Cancer Center & Research Institute. The speakers will provide a disease overview of HR-MDS, including current therapies and approach to patient management, evaluation of patient outcomes in HR-MDS trials, and the emerging treatment landscape and ongoing areas of unmet need. In addition, members of Syros’ leadership team will provide an overview of RARA overexpression and tamibarotene’s mechanism of action, review the design of the pivotal SELECT-MDS-1 Phase 3 trial, and discuss previously presented clinical data supporting the development of tamibarotene for HR-MDS and the potential commercial opportunity.

There will be an opportunity for Q&A during the presentation. Participants can register for the live webcast here. For participants joining via conference call, please dial (800) 549-8228 (domestic) or (646) 564-2877 (international) and refer to conference ID 68622. In addition, a live webcast of the presentation will be available on the Investors & Media section of the Syros website at www.syros.com. An archived replay of the webcast will be available following the presentation.

On June 13, 2024 Sonnet BioTherapeutics Holdings, Inc. (NASDAQ:SONN) (the "Company" or "Sonnet"), a clinical-stage company developing targeted immunotherapeutic drugs, reported the generation and in vitro characterization of two novel drug candidates, SON-1411 (IL18BPR-FHAB-IL12) and SON-1400 (IL18BPR-FHAB), each containing a modified version of recombinant human interleukin-18 (IL-18BPR). SON-1411 is a proprietary bifunctional fusion protein consisting of IL-18BPR combined with single-chain wild-type IL-12, linked to Sonnet’s Fully Human Albumin Binding (FHAB) platform, which will replace SON-1410 as a development target (Press release, Sonnet BioTherapeutics, JUN 13, 2024, View Source [SID1234644307]). SON-1400 is a monofunctional fusion protein comprising the same IL-18BPR domain linked to the FHAB. FHAB extends the half-life and biological activity of linked molecules by binding native albumin in the serum and targets the tumor microenvironment (TME) through high affinity binding to glycoprotein 60 (gp60) and the Secreted Protein Acidic and Rich in Cysteine (SPARC).

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IL-18 can regulate both innate and adaptive immune responses through its effects on natural killer (NK) cells, monocytes, dendritic cells, T cells, and B cells. IL-18 acts synergistically with other pro-inflammatory cytokines to promote interferon-γ (IFN-γ) production by NK cells and T cells. Systemic administration of IL-18 has been shown to have anti-tumor activity in several animal models. Moreover, tumor-infiltrating lymphocytes (TILs) express more IL-18 receptors than other T cells. However, IL-18 clinical trials have shown that, although it is well tolerated, IL-18 has poor efficacy in the treatment of cancers, most likely due in large part to the high co-expression of IL-18 binding protein (IL-18BP) in the TME. In particular, IL-18BP serves as a "decoy receptor" that binds to IL-18 with higher affinity, compared with the IL-18Rc complex, thereby causing a negative feedback loop with IL-18 and inhibiting IL-18-mediated TIL activation. Thus, there exists a potential for the discovery of IL-18 variant compositions that could harness the therapeutic potential of IL-18 for the treatment of cancers.

Sonnet’s strategy for amino acid modifications to rIL-18 was based on a compilation of literature review, 3D X-ray crystallography structures, and computer modeling analysis. Subsequently, certain IL-18 variant sequences were synthesized, engineered into expression constructs and manufactured at small scale in either CHO cell culture or E. coli. Highly purified milligram quantities of SON-1411 or SON-1400 were analyzed in vitro for IL-18Rc or IL-18BP binding activities, respectively, using the HEK-Blue and Bright-Glo Luciferase IL-18Rc reporter assays. In vitro results for at least one variant of IL-18 showed equivalent binding to the IL-18 Rc, compared to the wild-type IL-18 reference molecule, concomitant with no or reduced binding to IL-18BP.

"The development of a modified IL-18 has been a challenging scientific achievement. IL-18 is a key cytokine that, when combined synergistically with IL-12, has the potential to be an important therapeutic asset for oncology and cell-based therapy. We believe that these novel molecules combined with our proprietary FHAB platform are expected to demonstrate tumor targeting and longer half-lives, which in turn are expected to allow a therapeutic window for commercialization of these important oncology candidates", said Pankaj Mohan, Ph.D., Sonnet Founder and Chief Executive Officer.

"The known MOA of IL-18 inhibition by IL-18BP is reviving the importance of clinical applications of IL-18. IL-18BP has been shown to be elevated in cancer patients, thus negating the clinical use of IL-18. Sonnet is excited about the development of a novel bifunctional cytokine molecule, IL18BPR-FHAB-IL12, which contains a unique IL18 domain that does not bind the inhibitor IL-18BP but still maintains full IL-18 and IL-12 bioactivity. The clinical application of this bifunctional fusion protein could potentially expand immunotherapy applications for cancer patients" commented John Cini, Ph.D., Sonnet Chief Scientific Officer.

About SON-1411

SON-1411 is a candidate immunotherapeutic recombinant drug that is closely related to and will replace SON-1410, which links an unmodified single-chain human IL18 and an unmodified IL-12 with the albumin-binding domain of the single-chain antibody fragment A10m3. The only difference between SON-1410 and SON-1411 is that in the latter, the IL-18 domain has been modified via mutagenesis to retain wildtype binding to the IL-18 receptor (IL-18 Rc) while inhibiting or abolishing binding to the IL-18 binding protein (IL-18 BP). The A10m3 scFv was selected to bind both at normal pH, as well as at the acidic pH that is typically found in the TME. The FHAB technology targets tumor and lymphatic tissue, providing a mechanism for dose sparing and an opportunity to improve the safety and efficacy profile of IL-18 and IL-12, as well as a variety of potent immunomodulators that can be added using the platform. Interleukin-12 can orchestrate a robust immune response to many cancers and pathogens. Given the types of proteins induced in the TME, such as SPARC and gp60, several types of cancer such as non-small cell lung cancer, melanoma, head and neck cancer, sarcoma, and some gynecological cancers are particularly relevant for this approach. SON-1411 is designed to deliver IL-18BPR and IL-12 to local tumor tissue, turning ‘cold’ tumors ‘hot’ by stimulating IFNγ, which activates innate and adaptive immune cell responses and increases the production of Programed Death Ligand 1 (PD-L1) on tumor cells.

On June 13, 2024 Rezolute, Inc. (Nasdaq: RZLT) ("Rezolute" or the "Company"), a late-stage biopharmaceutical company committed to developing novel, transformative therapies for serious rare diseases, reported that it is commencing an underwritten public offering of shares of its common stock (or pre-funded warrants to purchase its common stock in lieu thereof) (Press release, Rezolute, JUN 13, 2024, View Source [SID1234644306]). In addition, the Company intends to grant the underwriters an option for a period of 30 days to purchase up to an additional 15 percent of the number of shares of its common stock plus the shares of common stock underlying pre-funded warrants sold in connection with the public offering. The public offering is subject to market and other conditions, and there can be no assurance as to whether or when the public offering may be completed or as to the actual size or terms of the public offering. All of the shares in the public offering are being offered by the Company.

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Jefferies and Cantor are acting as the book-running managers for the public offering.

A shelf registration statement on Form S-3 (File No. 333-275562) relating to the securities to be offered in the public offering was filed with the Securities and Exchange Commission (the "SEC") and was declared effective on November 29, 2023. The public offering will be made only by means of a prospectus supplement and accompanying prospectus that form a part of the registration statement. A preliminary prospectus supplement related to the public offering will be filed with the SEC and, when available, may be obtained on the SEC’s website at www.sec.gov. Copies of the preliminary prospectus supplement and accompanying prospectus relating to the public offering, when available, may be obtained by contacting: Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, New York, New York 10022, by telephone at 877-821-7388, or by email at [email protected] or Cantor Fitzgerald & Co., Attention: Capital Markets, 110 East 59th Street, 6th Floor, New York, New York 10022, or by email at [email protected]

This press release does 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 jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On June 13, 2024 Replimune Group, Inc. (Nasdaq: REPL), a clinical stage biotechnology company pioneering the development of a novel class of oncolytic immunotherapies, reported that it has entered into a securities purchase agreement for a private investment in public equity ("PIPE") that is expected to result in gross proceeds of approximately $100 million to the Company before deducting placement agent fees and offering expenses (Press release, Replimune, JUN 13, 2024, View Source [SID1234644305]). The financing was led by a life-sciences focused institutional investor, with participation from Redmile Group, RTW Investments, Boxer Capital and other institutional investors, including a leading mutual fund.

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Pursuant to the terms of the securities purchase agreement, Replimune will issue and sell to the investors an aggregate of 5,668,937 shares of its common stock ("Common Stock") at a price of $8.82 per share of Common Stock and pre-funded warrants to purchase 5,669,578 shares of Common Stock at a price of $8.819 per pre-funded warrant. The pre-funded warrants have an exercise price of $0.001 per share. The financing is expected to close on or about June 14, 2024, subject to satisfaction of customary closing conditions.

The Company intends to use the proceeds of the PIPE financing to fully scale up for the commercialization of RP1 in skin cancers thereby creating a potential path to profitability, and for working capital and general corporate purposes.

Leerink Partners acted as sole placement agent for the PIPE financing.

The offer and sale of the foregoing securities, including the shares of common stock issuable upon exercise of the pre-funded warrants, are being made in a transaction not involving a public offering and such securities have not been registered under the Securities Act of 1933, as amended, and may not be reoffered or resold in the United States except pursuant to an effective registration statement or an applicable exemption from the registration requirements. In connection with the securities purchase agreement, Replimune and the investors will enter into a registration rights agreement pursuant to which Replimune has agreed to file a registration statement with the Securities Exchange Commission (the "SEC") to register the resale by the investors of the shares of common stock and the shares of common stock issuable upon exercise of the pre-funded warrants sold in the PIPE financing. Any offering of the common stock under the resale registration statement will only be made by means of prospectus.

This press release shall not constitute an offer to sell or a solicitation of an offer to buy any common stock, pre-funded warrants, or any other securities of Replimune, nor shall there be any sale of such 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 June 13, 2024 Pasithea Therapeutics Corp. (NASDAQ: KTTA) ("Pasithea" or the "Company"), a clinical-stage biotechnology company developing PAS-004, a next-generation macrocyclic MEK inhibitor, for the treatment of neurofibromatosis type 1 (NF1) and other indications, reported that an independent Safety Review Committee (SRC) has completed its safety review of data from the first dose cohort (2mg) treated in the ongoing Phase 1 clinical trial (NCT06299839) of PAS-004 in patients with MAPK pathway driven advanced solid tumors with a documented RAS, NF1 or RAF mutation or patients who have failed BRAF/MEK inhibition (Press release, Pasithea Therapeutics, JUN 13, 2024, View Source [SID1234644304]).

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Based on these findings, the SRC recommended that the trial escalate to the next dose level (4mg) without modifications. This recommendation was based on the absence of any dose limiting toxicities (DLT’s) or clinically relevant treatment-emergent adverse events in the initial cohort of 3 patients. The Company has now completed enrollment and initial dosing of 3 patients in the second cohort.

Dr. Tiago Reis Marques, Chief Executive Officer of Pasithea stated, "We are pleased to have rapidly enrolled and completed first dosing of the participants in the second cohort following the SRC’s positive recommendation to advance to 4mg of PAS-004. We look forward to continuing to develop PAS-004 as a potential treatment for solid tumors as well as cutaneous and plexiform neurofibromas in NF1 patients. We remain on track to present our initial safety and pharmacokinetic (PK) data in the third quarter of 2024."

The Phase 1 trial is a multicenter, open-label, dose escalation study evaluating the safety, tolerability, and pharmacokinetics (PK) and pharmacodynamics (PD) of PAS-004 in patients with MAPK pathway driven advanced solid tumors with a documented RAS, NF1 or RAF mutation or patients who have failed BRAF/MEK inhibition. The primary objective of the study is to assess the safety and tolerability of PAS-004, with secondary objectives including PK and PD parameters, an evaluation of the preliminary anticancer activity (efficacy) of PAS-004 and defining the preliminary recommended Phase 2 dose(s).