On March 6, 2024 OnCusp Therapeutics, Inc., a clinical stage biopharmaceutical company dedicated to transforming cutting-edge preclinical innovation into clinically validated treatments for cancer patients worldwide, reported that the first patient has been dosed in the Phase 1 study evaluating CUSP06 for the treatment of platinum-refractory/resistant ovarian cancer and other advanced solid tumors (Press release, OnCusp Therapeutics, MAR 6, 2024, View Source [SID1234640879]).

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!

CUSP06 is engineered to increase potency, heighten the "bystander effect," elevate linker stability, and overcome drug resistance. Thus, it is a potentially safer and more effective therapeutic option for patients with advanced solid tumors that express Cadherin-6 (CDH6). Preclinical data further suggest that CUSP06 may demonstrate best-in-class activity in the clinic.

"We are thrilled to announce the initiation of the Phase 1 clinical trial for CUSP06, our first ADC program to enter the clinic, and look forward to seeing our robust preclinical findings reflected in clinical settings," stated Bing Yuan, PhD, Co-Founder and CEO of OnCusp Therapeutics. "This marks a pivotal moment for OnCusp as we transition into a clinical-stage company, reaffirming our dedication to delivering innovative therapies to patients in need."

Eric Slosberg, PhD, Co-Founder and Chief Development Officer of OnCusp Therapeutics, said "CDH6 is an ideal target for an ADC approach, as it is overexpressed in many cancer types such as ovarian, renal, cholangiocarcinoma, uterine, and other malignancies, but has limited expression in non-tumor tissues. We look forward to exploring the effect of CUSP06 in patients with both high and low CDH6 expressing tumors."

The Phase 1 multicenter study will evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of CUSP06 in adults with platinum-refractory/resistant ovarian cancer and other advanced solid tumors (NCT06234423). Phase 1a will determine safety and the recommended dose for expansion and the Phase 1b portion will focus on further characterizing safety and efficacy in selected tumor types.

"Ovarian cancer is the third most common and the most lethal gynecologic cancer worldwide," said Alexander Spira, MD, PhD, FACP, FASCO, CEO and Clinical Director for NEXT Oncology Virginia and a Principal Investigator for the Phase 1 study of CUSP06. "There is significant unmet medical need in the treatment landscape, especially in the platinum-resistant setting. We are excited to participate in this clinical trial and evaluate the potential of CUSP06 in treating ovarian cancer and other advanced solid tumors."

About CUSP06

CUSP06, a CDH6 ADC, is composed of a proprietary antibody with high CDH6 binding affinity, a protease-cleavable linker, and an exatecan payload (a potent and clinically validated topoisomerase-1 inhibitor). The linker is designed to complement the exatecan payload, enabling a stable and homogenous ADC. The payload is a weak substrate for BCRP/P-gp, which are drug efflux pumps that drive chemoresistance to many therapies. In preclinical data, this linker-payload has been shown to have an increased "bystander effect" compared to competitor ADCs. CUSP06 has a drug-to-antibody ratio of eight. OnCusp obtained the exclusive global rights (outside of China) to lead the development and commercialization of CUSP06 from Multitude Therapeutics.

On March 6, 2024 Avid Bioservices, Inc. (NASDAQ:CDMO), a dedicated biologics contract development and manufacturing organization (CDMO), reported the pricing of $160 million aggregate principal amount of 7.00% Convertible Senior Notes due 2029 (the "2029 Notes") (Press release, Avid Bioservices, MAR 6, 2024, https://ir.avidbio.com/news-releases/news-release-details/avid-bioservices-announces-pricing-private-placement-convertible [SID1234640877]). In connection with the offering, the company entered into private placement purchase agreements with the several purchasers, each of whom is a "qualified institutional buyer" within the meaning of Rule 144A promulgated under the Securities Act of 1933, as amended (the "Securities Act"). The closing of the offering is subject to customary closing conditions and is expected to take place on March 12, 2024.

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 2029 Notes will represent senior unsecured obligations of the company and will accrue interest payable semiannually in arrears on March 1 and September 1 of each year, beginning on September 1, 2024. The notes will mature on March 1, 2029, unless earlier converted or repurchased.

Before September 1, 2028, holders will have the right to convert their 2029 Notes only upon the satisfaction of specified conditions and during certain periods. On or after September 1, 2028 until the close of business on the second scheduled trading day immediately preceding the maturity date, holders may convert all or any portion of their 2029 Notes at any time. Upon conversion, the company will pay or deliver, as the case may be, cash, shares of its common stock or a combination of cash and shares of its common stock, at its election. The conversion rate for the 2029 Notes will initially be 101.1250 shares of the company’s common stock per $1,000 principal amount of notes (equivalent to an initial conversion price of approximately $9.89 per share of the company’s common stock). The initial conversion price represents a premium of approximately 12.5% over the last reported sale price of $8.79 per share of the company’s common stock on March 6, 2024. The conversion rate will be subject to adjustment in some events but will not be adjusted for any accrued or unpaid interest.

The 2029 Notes are not redeemable and no sinking fund is provided for the 2029 Notes. If the company undergoes a "fundamental change" (as defined in the indenture that will govern the 2029 Notes), then, subject to certain conditions and limited exceptions, holders may require the company to repurchase for cash all or any portion of their 2029 Notes at a fundamental change repurchase price equal to 100% of the principal amount of the 2029 Notes to be repurchased, plus accrued and unpaid interest to, but excluding, the fundamental change repurchase date. In addition, following certain corporate events that occur prior to the maturity date, the company will, in certain circumstances, increase the conversion rate for a holder who elects to convert its 2029 Notes in connection with such a corporate event.

The company expects to use the net proceeds from the Offering (i) to repurchase for cash a portion of its 1.250% Exchangeable Senior Notes due 2026 (the "2026 Notes") in privately negotiated transactions from certain noteholders and (ii) to the extent there are 2026 Notes outstanding after such repurchase, to repay in full any remaining outstanding 2026 Notes by depositing the required payoff amount with the trustee under the indenture of the 2026 Notes.

The 2029 Notes and any shares of the company’s common stock issuable upon conversion of the 2029 Notes have not been and will not be registered under the Securities Act, any state securities laws or the securities laws of any other jurisdiction, and unless so registered, may not be offered or sold in the United States absent registration or an applicable exemption from, or in a transaction not subject to, the registration requirements of the Securities Act and other applicable securities laws.

This press release is neither an offer to sell nor a solicitation of an offer to buy any of these securities nor shall there be any sale of these securities in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful prior to the registration or qualification thereof under the securities laws of any such state or jurisdiction. Further, this press release is not an offer to repurchase the 2026 Notes. As described in the Current Report on Form 8-K filed by the company on March 6, 2024, all of the 2026 Notes have been accelerated and became due and payable pursuant to an acceleration notice the company received from a holder of the 2026 Notes on February 29, 2024.

On March 6, 2024 Gilead Sciences, Inc. (Nasdaq:GILD) and Merus N.V. (Nasdaq:MRUS) reported a research collaboration, option and license agreement to discover novel dual tumor-associated antigens (TAA) targeting trispecific antibodies (Press release, Gilead Sciences, MAR 6, 2024, View Source [SID1234640876]). Gilead and Merus agreed to collaborate on the use of Merus’ proprietary Triclonics platform along with Gilead’s oncology expertise to research and develop multiple, separate preclinical research programs.

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!

Merus is a clinical-stage oncology company developing innovative, full-length, multispecific antibodies (Biclonics and Triclonics), referred to together as Multiclonics, that are generated by a proprietary common light chain technology. The Triclonics or trispecific platform provides the unique opportunity to design antibodies capable of simultaneously binding to three targets at once.

"We have seen the successful application of bispecific antibodies as an immune-modulating modality used to treat cancer. We are now looking ahead to the development of additional multispecific antibodies capable of driving robust anti-tumor immune responses with an improved efficacy and safety profile," said Flavius Martin, M.D., Executive Vice President, Research, Gilead Sciences. "We are excited to explore the potential of Merus’ differentiated Triclonics platform to discover and advance transformative new cancer therapies as we deepen our portfolio across oncology indications."

"We are looking forward to working with Gilead to develop novel T-cell engager antibodies using our Triclonics technology," said Hui Liu, Ph.D., Executive Vice President, Chief Business Officer & Head of Merus US. "We are grateful for our collaborations which represent opportunities for Merus to leverage our research capabilities to pursue innovative biology and to address significant unmet medical needs. Importantly, this collaboration represents the first for our proprietary Triclonics platform."

Terms of the Agreement

Under the terms of the agreement, Merus will lead early-stage research activities for two programs, with an option to pursue a third. Gilead will have the right to license programs developed under the collaboration after the completion of select research activities. If Gilead exercises its option to license any such program from the collaboration, Gilead will be responsible for additional research, development and commercialization activities for such program. Merus will receive an upfront cash payment of $56 million for initial targets as well as an equity investment by Gilead of $25 million in Merus common shares. Across all potential programs, Merus is also eligible to receive up to $1.5 billion including additional near term and option payments, potential development and commercialization milestones, as well as tiered royalties ranging from the mid-single to low-double digits on product sales should Gilead successfully commercialize a therapy from the collaboration. For the third potential program, Merus may opt-in to share 50/50 split of net profits and net losses, in lieu of future milestone and royalty payments.

Gilead does not exclude acquired IPR&D expenses from its non-GAAP financial measures. This transaction with Merus is expected to reduce Gilead’s GAAP and non-GAAP 2024 EPS by approximately $0.03 – $0.05.

On March 6, 2024 iTeos Therapeutics, Inc. (Nasdaq: ITOS), a clinical-stage biopharmaceutical company pioneering the discovery and development of a new generation of immuno-oncology therapeutics for patients, reported financial results for the fourth quarter and full year ended December 31, 2023 and provided a business update (Press release, iTeos Therapeutics, MAR 6, 2024, View Source [SID1234640875]).

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!

"As we anticipate four clinical readouts across the portfolio, 2024 is poised to be a transformative year for iTeos," said Michel Detheux, Ph.D., president and chief executive officer of iTeos. "With the recent developments in the TIGIT field, we believe belrestotug is in an advantageous position and are excited for its future prospects. We look forward to sharing updates from our Phase 2 trials focused on 1L NSCLC and 1L HNSCC in 2024. Additionally, our strong comprehension of the adenosine pathway has enabled us to develop two innovative and optimized assets – inupadenant, an A2AR antagonist in a class of its own, and EOS-984, a potential first-in-class inhibitor targeting the novel mechanism of ENT1. With our strategic cash position and robust pipeline, we are focused on the execution of these clinical trials to deliver on our highly anticipated milestones this year."

Corporate Developments

On March 6, 2024, iTeos announced the appointment of Jill DeSimone to the Company’s Board of Directors. With over 40 years of global business expertise in life sciences, Ms. DeSimone is recognized for her role as President of U.S. Oncology at Merck & Co., Inc., where she established the company’s oncology division, growing it from less than $500 million in annual revenue to $9 billion in eight years.
On December 7, 2023, iTeos announced the appointment of David K. Lee to the Company’s Board of Directors. A seasoned pharmaceutical veteran with a proven track record of building successful businesses focused on oncology and rare diseases, Mr. Lee currently serves as the Chief Executive Officer of Servier Pharmaceuticals (U.S.), where he established and grew Servier Pharmaceuticals to a fully innovative oncology company with four commercialized products and a robust pipeline.
Program Highlights

Belrestotug (EOS-448/GSK4428859A): IgG1 anti-TIGIT monoclonal antibody targeting first-line non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC) in collaboration with GSK

Preparation underway for Phase 3 registrational studies that will evaluate the belrestotug + dostarlimab doublet
GALAXIES Lung-201: topline data from Phase 2 platform trial assessing belrestotug + dostarlimab doublet in first-line advanced/metastatic NSCLC anticipated in 2024
GALAXIES H&N-202: enrollment ongoing in Phase 2 platform study assessing belrestotug + dostarlimab doublet and a triplet with GSK’s investigational anti-CD96 antibody (GSK’608) in first-line patients with PD-L1 positive recurrent / metastatic HNSCC
TIG-006 HNSCC: topline data from Phase 2 expansion trial assessing belrestotug + dostarlimab doublet in first-line PD-L1 positive advanced or metastatic HNSCC anticipated in 2024
TIG-006 mNSCLC: enrollment ongoing in Phase 1b expansion trial assessing belrestotug, dostarlimab, and chemotherapy triplet in first-line advanced or metastatic NSCLC
Continued advancement of Phase 1b trials exploring two novel triplets in advanced solid tumors: belrestotug + dostarlimab and GSK’s investigational anti-CD96 antibody (GSK’608), and belrestotug + dostarlimab and GSK’s investigational anti-PVRIG antibody (GSK’562)
Adenosine Pathway

Inupadenant (EOS-850): insurmountable small molecule antagonist targeting adenosine A2A receptor in second-line NSCLC

A2A-005: Data from the dose escalation portion of the Phase 2 trial with inupadenant and platinum-doublet chemotherapy in post-IO metastatic non-squamous NSCLC anticipated in late 2024.
EOS-984: first-in-class small molecule inhibiting equilibrative nucleoside transporter 1 (ENT1), a dominant transporter of adenosine on lymphocytes involved in T cell metabolism, expansion, effector function, and survival

Completed enrollment of the third dose cohort and continued advancement in the dose escalation of the Phase 1 trial in advanced malignancies
Abstract acceptance by The American Association for Cancer Research (AACR) (Free AACR Whitepaper) for EOS-984, which highlights preclinical data on the novel mechanism of action, monotherapy activity, and combination activity with anti-PD-1 therapy
Oral presentation by Matthew Vander Heiden, M.D., Ph.D., from the Koch Institute for Integrative Cancer Research in collaboration with iTeos Therapeutics on the role of ENT1 on the metabolism and the immune system in cancer at The SITC (Free SITC Whitepaper) Spring Scientific, Metabolism at the Hub of Cancer and Immunity in Miami, FL
Session: Influence of Nutrient Environment on Immune Response
Date and Time: Sunday, March 10, 2024, 9:10 AM – 10:10AM

Topline data from the Phase 1 trial anticipated in the second half of 2024
Fourth Quarter and Full Year 2023 Financial Results

Cash and Investment Position: The Company’s cash, cash equivalents, and investments position was $632.7 million as of December 31, 2023, as compared to $731.4 million as of December 31, 2022. The Company continues to expect its cash balance to provide runway through 2026.

Research and Development (R&D) Expenses: R&D expenses were $27.9 million for the fourth quarter and $113.3 million for the year ended December 31, 2023, as compared to $25.4 million for the fourth quarter and $97.4 million for the year ended December 31, 2022. The increases in each comparative period were primarily due to increases in activities related to the belrestotug, inupadenant, and EOS-984 programs, and included the addition of new R&D employees hired to help advance these programs.

General and Administrative (G&A) Expenses: G&A expenses were $12.4 million for the fourth quarter and $50.4 million for the year ended December 31, 2023, as compared to $11.1 million for the fourth quarter and $43.9 million for the year ended December 31, 2022. The increases were primarily due to increases in headcount and related costs and an increase in stock-based compensation compared to the prior year. The increases were partially offset by a decrease in recruiting costs.

Net Income/Loss: Net loss attributable to common shareholders was $30.6 million, or net loss of $0.85 per basic and diluted share for the quarter ended December 31, 2023, as compared to a net income of $20.5 million, or a net income of $0.57 per basic share and $0.54 per diluted share for the quarter ended December 31, 2022. Net loss was $112.6 million, or net loss of $3.15 per basic and diluted share, for the year ended December 31, 2023, as compared to a net income of $96.7 million, or net income of $2.72 per basic share and $2.56 per diluted share, for the year ended December 31, 2022.

On March 6, 2024 Medigene AG (Medigene or the "Company", FSE: MDG1, Prime Standard), an immuno-oncology platform company focusing on the discovery and development of T cell immunotherapies for solid tumors, reported that it will present a poster at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (AACR) (Free AACR Whitepaper) 2024 taking place from April 5-10, 2024 in San Diego, USA as well as an oral presentation at the ELRIG-Forum 2024 to be held in Darmstadt, Germany on March 7, 2024 (Press release, MediGene, MAR 6, 2024, View Source [SID1234640873]).

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!

Poster presentation:

AACR 2024
View Source
Location: San Diego Convention Center, San Diego
Date: April 5-10, 2024

Details on the poster presentation are as follows:
Abstract title: TCR-gated control of costimulatory switch protein (CSP) activation in rTCR-T cells expressing PD1-41BB
Maja Buerdek, Petra U. Prinz, Kathrin Mutze, Andrea Coluccio, Stefanie Tippmer, Miriam Bosch, Giulia Longinotti, Mario Catarinella, Kathrin Davari, Christiane Geiger, Barbara Loesch, Kristy Crame, Dolores J. Schendel.
Session details: PO.IM01.13 – Adoptive Cell Therapies 1: Tumor Antigen-Specific T-cells and TCR-T, Sunday, April 7, 1:30 PM – 5:00 PM local time

The work to be presented shows that recombinant T cell receptor engineered T cells (rTCR-T cells), when armored and enhanced by the PD1-41BB CSP, exhibit superior TCR-T cell functionality and safety as well as a favorable safety profile, revealing the strong potential for improving treatment of cancer patients suffering from advanced solid tumor malignancies.

The abstract for this research has been published online at View Source!/20272/presentation/6084 and the poster will be available online after the conference at View Source." target="_blank" title="View Source." rel="nofollow">View Source

The Company is planning a first-in-human trial for MDG1015, a TCR-T therapy incorporating the CSP in gastric cancer, ovarian cancer, myxoid/round cell liposarcoma and synovial sarcoma with IND/CTA filing targeted for 2H 2024. MDG1015 is a first-in-class, third generation TCR-T therapy targeting NY-ESO-1/ LAGE-1a, armored and enhanced by the PD1-41BB CSP.

Oral presentation:

ELRIG-Forum 2024
View Source
Location: Darmstadtium Convention Centre, Darmstadt
Date and time: March 7, 2024, 11:10 – 11:30am local time
Presenter: Dr. Barbara Lösch, Head, Technology & Innovation
Title: Evolution by Innovation: Connecting the Dots of TCR-T Therapies

Dr. Lösch will provide an overview on the Company’s proprietary End-to-End (E2E) Platform and highlight various tools within the E2E Platform that can enhance TCR-T cell functionality, safety and efficacy for generation of best-in-class, differentiated TCR-T therapies.

This presentation will available on Medigene’s website on March 7, 2024: View Source