On October 24, 2024 Tyra Biosciences, Inc. (Nasdaq: TYRA), a clinical-stage biotechnology company focused on developing next-generation precision medicines that target large opportunities in Fibroblast Growth Factor Receptor (FGFR) biology, reported clinical proof-of-concept data for TYRA-300 in patients with metastatic urothelial (mUC) cancer from its ongoing SURF301 Phase 1/2 study (Press release, Tyra Biosciences, OCT 24, 2024, View Source [SID1234647378]). These data will be presented in a late-breaking oral presentation at the 36th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) (ENA) Symposium on Molecular Targets and Cancer Therapeutics, being held October 23-25, 2024 in Barcelona, Spain. TYRA-300 is a potential first-in-class, investigational, oral, FGFR3-selective inhibitor designed to avoid the toxicities associated with inhibition of FGFR1, FGFR2 and FGFR4, while being agnostic for the FGFR3 gatekeeper mutations.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"FGFR3 alterations are known to drive tumor biology in a subset of urothelial cancer. While pan-FGFR inhibitors have demonstrated benefit and are approved for use in FGFR3 altered urothelial cancer, they are associated with multiple intolerable on-target toxicities that limit their clinical utility. There remains an unmet need to deliver improved precision medicine for urothelial cancer patients, that allow patients to not only live longer, but live better," said Ben Tran, M.D., Associate Professor, Peter McCallum Cancer Centre, Melbourne, Australia. "The initial results from TYRA-300 are very encouraging. I believe TYRA-300 has the potential to be a next generation targeted therapy, with high selectivity for FGFR3. These early data provide support that TYRA-300 can deliver improved anti-tumor activity and tolerability for our FGFR3 altered urothelial cancer patients. TYRA-300 has real potential to improve outcomes, and I look forward to its continued development in all FGFR3 altered cancers."

Summary of Interim Clinical Results

As of August 15, 2024, the data cutoff date, 41 patients were enrolled in the Phase 1 portion of the SURF301 Phase 1/2 study. Eligible participants were adults with advanced malignancies with or without FGFR3 alterations, including those with prior treatment with erdafitinib. The enrolled patient population was heavily pre-treated, with 44% of patients receiving ≥ 3 lines of therapy prior to receiving TYRA-300, and 76% of FGFR3+ mUC patients receiving ≥ 3 lines of therapy. Treatment with TYRA-300 was evaluated across six dose levels, ranging from 10 mg-120 mg once daily (QD).

Preliminary PK/PD analysis in 41 patients as of the data cutoff date: TYRA-300 plasma concentrations indicate adequate target coverage at ≥ 90 mg QD, with further pharmacokinetic characterization ongoing.

In patients with FGFR3+ mUC who received doses ≥ 90 mg QD, anti-tumor activity was observed in all patients:
6 out of 11 (54.5%) patients at ≥ 90 mg QD achieved a PR, 3 of which are still ongoing.
5 out of 10 (50%) patients at 90 mg QD achieved a PR.
1 out of 1 (100%) patient at 120 mg QD achieved a PR.
A 100% disease control rate (DCR) was achieved for all patients at ≥ 90 mg QD (PR + stable disease).

TYRA-300 has demonstrated favorable interim safety results as of the data cutoff date:
Preliminary data from SURF301 suggest TYRA-300 to be generally well-tolerated, with infrequent FGFR2- and FGFR1-associated toxicities.
In doses from 10 mg up to 120 mg QD, there were 4 (10%) serious adverse events related to TYRA-300, 1 dose-limiting toxicity (DLT) of grade (Gr) 3 diarrhea at 90 mg QD, and 1 treatment-related adverse event (TRAE) leading to discontinuation of treatment (Gr3 ALT, 90 mg QD).
There were no ≥ Gr4 TRAEs.
The 120 mg QD dose was the highest dose evaluated with no DLTs reported.
"The preliminary data are what we were expecting to see with TYRA-300, being generally well-tolerated with fewer toxicities, and anti-tumor activity in FGRF3+ mUC patients," said Doug Warner, M.D., Chief Medical Officer of TYRA. "The emerging profile of TYRA-300 supports further development in metastatic urothelial cancer, where an attractive opportunity exists for a more tolerable option in second line."

Dr. Warner continued, "We are grateful for the support of our study participants, their families and our global collaborators on SURF301. We remain focused on progressing TYRA-300 through dose optimization in SURF301 and toward patients in need."

"Our team set out to solve an ambitious chemistry problem that had stumped the field of precision oncology – to create an efficacious FGFR3-selective inhibitor with a favorable tolerability profile to address the limitations of pan-FGFR inhibitors. We believe that today’s interim results provide clinical support for addressing this difficult problem, and the data are in line with our expectations," said Todd Harris, CEO of TYRA. "These data give us confidence to advance TYRA-300 through Part B in SURF301 and explore larger opportunities with Phase 2 studies in metastatic urothelial cancer, non-muscle invasive bladder cancer and achondroplasia."

ENA 2024 presentation details:

Title: "Preliminary safety and anti-tumor activity of TYRA-300, a highly selective FGFR3 inhibitor, in participants with advanced solid tumors with activating FGFR3 mutations/fusions (SURF301)"

Session: Late Breaking Abstracts and Proffered Papers: Novel discoveries in drug development
Date: Friday, October 25, 2024
Time: 15:36 – 15:48 hrs CEST
Abstract #: 500LBA

Conference Call Information

TYRA is hosting a conference call and webcast on October 25, 2024, at 8am ET to review the interim clinical proof-of-concept results demonstrated with TYRA-300 in mUC. Participants may access a live webcast of the call and the associated slide presentation on the "For Investors" page of the TYRA website at View Source To participate via telephone, please register in advance at this link. Upon registration, all telephone participants will receive a confirmation email detailing how to join the conference call, including the dial-in number along with a unique passcode and registrant ID that can be used to access the call. A replay of the conference call and webcast will be archived on the Company’s website for at least 30 days.

About TYRA-300 and the SURF301 Study

TYRA-300 is TYRA’s lead precision medicine program stemming from its in-house SNÅP platform. TYRA-300 is an investigational, oral, FGFR3-selective inhibitor currently in development for the treatment of cancer and skeletal dysplasias, including achondroplasia and hypochondroplasia. In oncology, TYRA-300 is being evaluated in a multi-center, open label Phase 1/2 clinical study, SURF301 (Study in Untreated and Resistant FGFR3+ Advanced Solid Tumors) (NCT05544552). The study is designed to determine the optimal and the recommended Phase 2 dose (RP2D) of TYRA-300, as well as to evaluate the preliminary anti-tumor activity of TYRA-300. Part A of the study included patients with all solid tumors who are FGFR3 +/-, and explored doses of TYRA-300 ranging from 10mg -120mg once-daily (QD). Part A of SURF301 is complete. The Company continues to advance TYRA-300 through dose expansion in Part B, which includes patients with solid tumors who are FGFR3+, to evaluate potentially therapeutic doses in preparation for potential future Phase 2 studies in metastatic urothelial carcinoma (mUC) and non-muscle invasive bladder cancer (NMIBC).

In skeletal dysplasias, TYRA-300 has demonstrated positive preclinical results in achondroplasia and hypochondroplasia. In July 2023 and January 2024, the FDA granted Orphan Drug Designation (ODD) and Rare Pediatric Designation (RPD) to TYRA-300, respectively, for the treatment of achondroplasia.

On October 24, 2024 iTeos Therapeutics, Inc. (Nasdaq: ITOS) ("iTeos"), a clinical-stage biopharmaceutical company pioneering the discovery and development of a new generation of immuno-oncology therapeutics for patients, reported that preclinical, translational, and clinical data from inupadenant will be presented at the European Society for Medical Oncology Immuno-Oncology (ESMO-IO) Congress 2024, being held December 11-13, 2024 in Geneva, Switzerland (Press release, iTeos Therapeutics, OCT 24, 2024, View Source [SID1234647376]). The clinical and translational data from the dose escalation portion of A2A-005, the Phase 2 trial assessing inupadenant and platinum-doublet chemotherapy in post-immunotherapy metastatic non-small cell lung cancer (NSCLC) patients, will be presented as mini oral presentations. Preclinical data from inupadenant will be presented in the poster session.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Mini Oral Presentation Details
Title: The A2AR Antagonist Inupadenant Promotes Humoral Responses in Patients
Abstract Number: 174MO
Session Title: Mini Oral Session 1
Date / Time: December 12, 2024 at 9:24 am CEST

Title: Inupadenant Combined with Chemotherapy in Patients with Non-Squamous NSCLC Progressing On or After Immune Checkpoint Inhibitor Therapy: Results from Dose-Finding Part of the A2A-005 Trial
Abstract Number: 120MO
Session Title: Mini Oral Session 2
Date / Time: December 12, 2024 at 14:55 pm CEST

Poster Presentation Details
Title: The A2AR Antagonist Inupadenant Promotes Humoral Responses in Preclinical Models
Abstract Number: 48P
Session Title: Poster Display Session
Date / Time: December 12, 2024 at 12:30 pm CEST

ESMO-IO indicates that all regular abstracts will be published on the ESMO (Free ESMO Whitepaper)-IO website on Thursday, December 5, 2024 at 00:05 am CEST.

On October 24, 2024 Mustang Bio, Inc. ("Mustang" or the "Company") (Nasdaq: MBIO), a clinical-stage biopharmaceutical company focused on translating today’s medical breakthroughs in cell therapies into potential cures for difficult-to-treat cancers, reported that it has entered into a definitive agreement for the exercise of certain existing warrants to purchase an aggregate of 16,877,638 shares of its common stock having an exercise price of $0.237 per share, originally issued in May 2024 (Press release, Mustang Bio, OCT 24, 2024, View Source [SID1234647375]). The issuance or resale of the shares of common stock issuable upon exercise of the existing warrants are registered pursuant to an effective registration statement on Form S-1 (File No. 333-278006). The gross proceeds to the Company from the exercise of the existing warrants are expected to be approximately $4 million, prior to deducting placement agent fees and offering expenses payable by the Company.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

H.C. Wainwright & Co. is acting as the exclusive placement agent for the offering.

In consideration for the immediate exercise of the existing warrants for cash, the Company will issue new unregistered warrants to purchase up to an aggregate of 33,755,276 shares of common stock. The new warrants will have an exercise price of $0.27 per share and will be exercisable commencing on the effective date of stockholder approval of the issuance of the shares issuable upon exercise of the new warrants (the "Stockholder Approval"). The new warrants to purchase 16,877,638 shares of common stock will have a term of five years from the Stockholder Approval, and the new warrants to purchase 16,877,638 shares of common stock have a term of twelve months from the Stockholder Approval.

The offering is expected to close on or about October 25, 2024, subject to satisfaction of customary closing conditions. Mustang currently intends to use the net proceeds from the offering for working capital and general corporate purposes.

The new warrants described above are being offered in a private placement under Section 4(a)(2) of the Securities Act of 1933, as amended (the "Securities Act"), and Regulation D promulgated thereunder and, along with the shares of common stock issuable upon exercise of the new warrants, have not been registered under the Securities Act, or applicable state securities laws. Accordingly, the new warrants issued in the private placement and the shares of common stock underlying the new warrants 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 covering the resale of the shares of common stock issuable upon the exercise of the new warrants.

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 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 October 24, 2024 Molecular Partners AG (SIX: MOLN; NASDAQ: MOLN), a clinical-stage biotech company developing a new class of custom-built protein drugs known as DARPin therapeutics ("Molecular Partners" or the "Company"), reported the pricing of an underwritten offering in the United States of 3,642,988 American Depositary Shares ("ADSs") representing 3,642,988 ordinary shares at an offering price of $5.49 per ADS, for total gross proceeds of approximately $20.0 million (Press release, Molecular Partners, OCT 24, 2024, View Source [SID1234647374]). All of the ADSs to be sold in the offering will be offered by Molecular Partners. The offering is expected to close on October 29, 2024, subject to customary closing conditions.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The offering included participation from a new investor HBM Healthcare Investments Ltd, which is a leading healthcare investor, as well as multiple existing investors. Leerink Partners and TD Cowen are acting as joint bookrunning managers for the offering. LifeSci Capital is acting as lead manager for the offering, with Zürcher Kantonalbank (ZKB) serving as settlement agent.

Molecular Partners currently intends to use the net proceeds from this offering, together with its existing cash and cash equivalents, for development and expansion of its radiopharmaceutical pipeline and platform (Radio-DARPin Therapeutics) and for working capital and other general corporate purposes.

The securities are being offered pursuant to an effective F-3 shelf registration statement that was previously filed with the Securities and Exchange Commission ("SEC"). A prospectus supplement will be filed with the SEC and will be available on the SEC’s website at www.sec.gov. The offering will be made only by means of a written prospectus and prospectus supplement that form a part of the registration statement. Copies of the prospectus supplement and the accompanying prospectus relating to the offering may be obtained, when available, for free from Leerink Partners LLC, Attention: Syndicate Department, 53 State Street, 40th Floor, Boston, Massachusetts 02109, by telephone at (800) 808-7525, ext. 6105, or by email at [email protected] or from TD Securities (USA) LLC, 1 Vanderbilt Avenue New York, New York 10017, by telephone at (855) 495-9846 or by email at [email protected].

The SIX Swiss Exchange ("SIX") has pre-approved, subject to certain customary conditions, the listing of the new ordinary shares underlying the ADSs on October 17, 2024. In connection with the listing of the new ordinary shares underlying the ADSs on the SIX, the registration statement on Form F-3, filed by the Company with the SEC together with the prospectus supplement constitute a foreign prospectus within the meaning of article 54 paras. 2 and 3 of the Swiss Financial Services Act of June 15, 2018 ("FinSA") and article 70 paras. 2-4 of the Swiss Financial Services Ordinance of November 6, 2019 ("FinSO"). The registration statement on Form F-3 has been deposited with and approved by the Prospectus Office of SIX Exchange Regulation and has been included as a foreign prospectus in the prospectus list published by the Prospectus Office of SIX Exchange Regulation. The prospectus supplement will be filed with the Prospectus Office.

This press release does not constitute an offer to sell or the solicitation of an offer to buy securities, and shall not constitute an offer, solicitation or sale in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of that jurisdiction. There is no intention to publicly offer, solicit, sell or advertise, directly or indirectly, any securities of Molecular Partners in or into Switzerland within the meaning of FinSA.

On October 24, 2024 Skyhawk Therapeutics, Inc., a clinical-stage biotechnology company developing novel small molecule therapies designed to modulate critical RNA targets, reported that the Company presented compelling preclinical data highlighting the therapeutic potential of its first-in-class compound, SKY-1214, at the European Organization for Research and Treatment of Cancer (EORTC)-National Cancer Institute (NCI)-American Association for Cancer Research (AACR) (Free AACR Whitepaper) Molecular Targets and Cancer Therapeutics Symposium ("EORTC-NCI-AACR" or the "Triple Meeting") (Press release, Skyhawk Therapeutics, OCT 24, 2024, View Source [SID1234647373]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

SKY-1214 is a first-in-class, oral RNA splicing modulator discovered through the company’s novel RNA-splicing platform and being developed for difficult-to-treat multiple myeloma (MM) and non-Hodgkin’s lymphoma (NHL). SKY-1214 targets FANCL/FANCI, critical components of the Fanconi anemia DNA damage repair pathway, which MM and NHL cells use to maintain their genome integrity.

Study authors concluded that SKY-1214 shows potent and efficacious anti-cancer activity in MM and NHL models in vitro, including in models with high-risk cytogenetic and/or genetic alterations (e.g., t(14;16), t(4;14), 1q+, and double-hit lymphoma). Additionally, in vivo treatment with SKY-1214 as a monotherapy resulted in tumor growth inhibition and regression to undetectable levels at tolerated doses in NHL and difficult-to-treat MM xenograft mouse models, including KMS-28BM.

"We’re excited to present these data and to introduce SKY-1214, our most-advanced oncology program, ready for IND submission," said Sergey Paushkin, M.D., Ph.D., Co-founder, Head of R&D at Skyhawk. "There are a number of approved treatments for both MM and NHL, but all patients with MM eventually progress and only 50% of patients with certain NHL subtypes can be cured, underscoring the urgent need for new therapies with novel mechanisms of action. SKY-1214’s profound anti-cancer activity, including in these high-risk tumor cell lines, supports further development and exploration as a single agent and in combination treatment in these difficult-to-treat cancers."

The poster is available on the Skyhawk website at www.skyhawktx.com/resources.

About SKY-1214

SKY-1214 is a first-in-class, oral FANCL/FANCI targeting RNA splicing modulator being developed for difficult to treat multiple myeloma (MM) and non-Hodgkin’s lymphoma (NHL). FANCL/FANCI are critical components of the Fanconi anemia DNA damage repair pathway, which MM and NHL tumor cells use to maintain their genome integrity. Skyhawk has observed anti-tumor activity for SKY-1214 in a number of preclinical cell models, including those representing prevalent high-risk cytogenetic alterations. SKY-1214 also demonstrated anti-tumor activity in human tumor cell-derived xenograft mouse models correlating with FANCL/FANCI mRNA reduction. SKY-1214 has completed IND-enabling studies.