On April 30, 2024 Repare Therapeutics Inc. ("Repare" or the "Company") (Nasdaq: RPTX), a leading clinical-stage precision oncology company, and Debiopharm (www.debiopharm.com), a privately-owned, Swiss-based biopharmaceutical company aiming to establish tomorrow’s standards of care to cure cancer and infectious diseases, reported that the first patient has been dosed in Module 4 of the ongoing Phase 1/1b MYTHIC (NCT04855656) clinical trial investigating lunresertib in combination with Debio 0123 (Press release, Repare Therapeutics, APR 30, 2024, View Source [SID1234642489]). In this trial, Debiopharm and Repare seek to assess the safety, pharmacokinetics, pharmacodynamics and preliminary clinical activity of this PKMYT1 and WEE1 inhibitor combination.

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In early January, Repare and Debiopharm announced a collaboration to evaluate the clinical combination of lunresertib, a first-in-class, selective and potent oral small molecule inhibitor of PKMYT1, and Debio 0123, an oral, brain-penetrant, highly selective WEE1 kinase inhibitor. This collaboration is based on preclinical in vivo data and other data showing rapid, remarkable tumor regressions and high predicted clinical tolerability and represents the first clinical-stage approach to inhibiting both PKMYT1 and WEE1.

"We are excited to have treated our first patient with lunresertib and Debio 0123," said Maria Koehler, MD, PhD, Executive Vice President and Chief Medical Officer of Repare. "Each of these compounds is well understood and clinically characterized. This combination provides us a unique opportunity to optimize dosing between two selective compounds and overcome limitations inherent to dual-inhibitor approaches. We expect this clinical collaboration will allow us to optimize the excellent synergy we saw preclinically to maximize patient benefit and tolerability."

"Lunresertib and Debio 0123 have the potential to be a transformative combination therapy for cancer patients with high unmet medical need," said Angela Zubel, Chief Development Officer of Debiopharm. "Treating the first patient in this new Module of the MYTHIC clinical trial is an important milestone for our collaboration, as it allows us to execute clinical development swiftly. We look forward to working closely with Repare to further characterize these innovative precision medicine therapies."

About Lunresertib

Lunresertib (RP-6306) is a first-in-class, selective and potent oral small molecule inhibitor of PKMYT1, a cancer target Repare discovered and identified as synthetic lethal with CCNE1 amplification, FBXW7 and PPP2R1A alterations in solid tumors. Lunresertib is currently the sole PKMYT1 inhibitor known to be in clinical trials and is being evaluated alone and in combinations across several studies in the US, UK/EU4, and Canada. Repare has presented positive initial Phase 1 data from its ongoing Phase 1/1b MYTHIC trial (NCT04855656) demonstrating proof of concept for lunresertib alone and in combination. In addition to being well tolerated and having a compelling safety profile, Repare presented anti-tumor activity for lunresertib in combination with camonsertib, an ATR inhibitor developed by Repare, expanded clinical studies for which are ongoing.

About Debio 0123

Debio 0123 is an oral, brain-penetrant, highly selective WEE1 kinase inhibitor. WEE1 is a key regulator of the G2/M and S phase checkpoints, activated in response to DNA damage and replication stress, allowing cells to repair their DNA before resuming their cell cycle. WEE1 inhibition, particularly in combination with DNA damaging agents, induces an accumulation of DNA damage and pushes the cells through cell cycle without DNA repair, promoting mitotic catastrophe and induction of apoptosis in cancer cells. Debio 0123 is currently being investigated in clinical trials in patients with solid tumors as a monotherapy and in combination. Debio 0123 is being developed to address high unmet needs of patients living with the burden of difficult-to-treat cancers.

On April 30, 2024 Arsenal Biosciences, Inc. (ArsenalBio), a clinical stage programmable cell therapy company focused on engineering advanced CAR T-cell therapies for solid tumors, reported that the first patient has been dosed with AB-2100 in a multi-center, open-label Phase 1/2 clinical trial for patients with clear-cell renal cell carcinoma (ccRCC) (Press release, ArsenalBio, APR 30, 2024, View Source [SID1234642488]). AB-2100 utilizes ArsenalBio’s CITE (CRISPR Integration of Transgenes by Electroporation) technology to engineer T cells to selectively target the tumor and overcome the suppressive tumor microenvironment. These engineering features will potentially enable the patient’s immune system to destroy ccRCC cells without harming normal tissues.

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"Kidney cancer is an immunologically responsive malignancy with several FDA approved immunotherapies on the market. But despite much progress in the field, there remains a tremendous unmet need in this indication, which we believe our Integrated Circuit T (ICT) cell technology is ideally suited to address," said Susie Jun, M.D., Ph.D., ArsenalBio’s Chief Medical Officer. "As with our AB-1015 program in ovarian cancer, we hope this study succeeds in identifying a safe and therapeutic dose to enable further study of this potential therapy in larger patient cohorts."

The Phase 1/2 trial (NCT06245915 ) is a dose escalation study that will evaluate the safety and efficacy of AB-2100 in patients with ccRCC that either came back or did not improve after treatment with a checkpoint inhibitor and a VEGF inhibitor. The goal of the study is to determine the maximum tolerated dose of AB-2100, which is administered intravenously via a single infusion following completion of conditioning chemotherapy. The study is expected to enroll up to 60 patients in Phase 1 and 130 patients total across multiple clinical sites in the United States.

AB-2100 is an ICT cell therapy engineered with the intent to treat ccRCC. The foundational manufacturing technique is precise and specific CRISPR-mediated insertion of a large synthetic double-stranded DNA cassette into a novel safe harbor site in Chromosome 11. The cassette encodes several features: a synthetic logic gate designed to optimize how the ICT cells target tumors and avoid normal tissues by requiring the presence of two distinct proteins in ccRCC (prostate-specific membrane antigen (PSMA) on tumor endothelium and carbonic anhydrase 9 (CA9) on the adjacent tumor cell); shRNAs to armor the T cell against immunosuppressive signals in the TME; and a novel synthetic pathway activator (SPA) designed to increase the potency and functional persistence of the engineered T cells.

"Our logic gate approach was designed to selectively target tumors and spare normal tissues by requiring the presence of two antigens in close proximity," said Dr. Jun. "Based upon our preclinical data we believe this synthetic biology-based logic gate approach will enable targeting of antigens like CA9 where conventional CAR T-cell strategies have been limited by on-target toxicity in healthy tissues."

AB-2100 is ArsenalBio’s second internally discovered T cell therapeutic candidate to enter clinical development. A multi-center, open-label phase 1 dose escalation trial (NCT05617755) of AB-1015, under investigation for the treatment of ovarian cancer, is currently enrolling.

On April 30, 2024 BostonGene, a leading provider of AI-driven molecular and immune profiling solutions, and the Parker Institute for Cancer Immunotherapy (PICI), a network of the largest concentration of immuno-oncology (IO) expertise in the world, reported the launch of a collaboration aimed at uncovering molecular mechanisms underlying IO treatment response and treatment-related toxicity in advanced cancer patients and discovering actionable blood-based biomarkers (Press release, BostonGene, APR 30, 2024, View Source [SID1234642487]).

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BostonGene will analyze longitudinal blood samples from PICI’s RADIOHEAD (Resistance Drivers for Immuno-Oncology Patients Interrogated by Harmonized Molecular Datasets) program, a prospective study of approximately 1,200 pan-cancer patients on standard of care immune checkpoint inhibitor treatment regimens. BostonGene’s revolutionary immunoprofiling incorporates flow cytometry and RNA-sequencing to track changes in the peripheral blood, which will be correlated with genetic variations from germline DNA testing to uncover blood-based signatures with immunotherapy response, resistance and toxicity.

"PICI’s mission-focused collaboration with BostonGene is a significant step toward unlocking the potential of blood-based biomarkers to advance personalized immunotherapy," said Tarak Mody, PhD, Chief Business Officer at PICI. "Through the generation of large multi-omic datasets and machine learning, we aim to provide the PICI Network and our partners with improved patient selection strategies and valuable insights that can accelerate discovery, target validation and clinical research."

"BostonGene’s AI-driven solutions combined with PICI’s unparalleled network of immuno-oncology expertise promise to redefine how we approach advanced cancer treatment. Together, we’re pioneering the search for blood-based biomarkers," said Nathan Fowler, MD, Chief Medical Officer at BostonGene.

On April 30, 2024 TriSalus Life Sciences Inc., (Nasdaq: TLSI), reported the closing of a debt financing facility for up to $50 million with OrbiMed, a healthcare investment firm (Press release, TriSalus Life Sciences, APR 30, 2024, View Source [SID1234642486]). The capital is expected to provide financial flexibility to support the execution of strategic expansion plans and fuel continued growth.

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Under the terms of the Credit Agreement (the "Credit Agreement") with OrbiMed, the Company borrowed $25 million at closing. In addition, an aggregate of up to an additional $25 million is available in two tranches at the Company’s option, based on the achievement of certain revenue thresholds. The Credit Agreement has a five-year term that matures in April 2029. In connection with the funding of the closing amount, the Company also issued OrbiMed a warrant to purchase 130,805 shares of the Company’s common stock, with an exercise price of $9.5562. Including the full funding in the Credit Agreement and current cash and cash equivalents on hand, the Company expects its cash runway will extend through 2025.

"We are excited to be partnering with OrbiMed," said Mary Szela, Chief Executive Officer of TriSalus Life Sciences. "This transaction provides us with the needed capital to execute strategic growth initiatives for TriNav, our Pressure Enabled Drug Delivery (PEDD) technology, which increases delivery of therapeutics in liver and pancreatic tumors. Additionally, this funding allows us to advance our technology pipeline as we continue to transform our business. We believe this financing provides us sufficient capital to reach break-even EBITDA for our TriNav business in 2025 and reduces the near-term need of equity financing."

Matthew Rizzo, General Partner of OrbiMed, added, "We are excited to support TriSalus Life Sciences as they pursue their strategic objectives, providing them with the necessary capital for financial flexibility, and enabling TriNav commercial and technology pipeline expansion."

TriSalus Life Sciences was represented in this transaction by Cantor Fitzgerald & Co., who served as sole placement agent and Cooley LLP, who served as legal counsel. OrbiMed was represented in this transaction by Covington & Burling LLP, who served as legal counsel.

On April 30, 2024 Medivir reported preparations for the planned phase 2b study continue according to plan after the completed Type C meeting with the FDA, strengthened by the fact that the median time to progression with fostrox + Lenvima increased to 7 months (Press release, Medivir, APR 30, 2024, View Source;interim-report-january–march-2024-302131228.html [SID1234642485]).

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January – March

Financial summary for the quarter

Net turnover amounted to SEK 0.5 (0.4) million.
The loss before interest, tax, depreciation and amortization (EBITDA) amounted to SEK -26.7 (-18.9) million. Basic and diluted earnings per share amounted to SEK -0.23 (-0.34) and SEK -0.23 (-0.34) respectively.
Cash flow from operating activities amounted to SEK -35.0 (-16.1) million.
Cash and cash equivalents at the end of the period amounted to SEK 153.4 (100.8) million
Significant events during the quarter

In January Tango Therapeutics announced that it has dosed the first patient with TNG348, a new USP1-inhibitor from the preclinical USP1 program in-licensed from Medivir in 2020.
Positive results from the ongoing phase 1b/2a study in advanced liver cancer (HCC) showing further improved response and time to progression were presented at the ASCO (Free ASCO Whitepaper) GI Symposium in San Francisco.
In January, a directed issue to Hallberg Management AB was carried out amounting to approximately SEK 20 million before deduction of issuance costs.
In February, a change in Medivir’s nomination committee announced as Anders Hallberg, appointed by Healthinvest Partners, leaves the nomination committee and is replaced by Stefan Bengtsson, appointed by CA Fastigheter AB.
Events after the end of the period

In April it was announced that Medivir’s partner Vetbiolix, a veterinary biotechnology company based in France, reported positive results from a proof-of-concept clinical trial in canine periodontitis with its drug candidate VBX-1000, formerly known as MIV-701.
In April it was announced that Medivir has completed a so-called Type C meeting with the FDA and that the company’s preparations for the planned phase 2b study are continuing as planned, with a couple of adjustments in study design with limited impact on the timeline and size of the study.
In April MIV-711 was granted Rare Pediatric Disease Designation (RPDD) and Orphan Drug Designation (ODD) from the FDA for the treatment of Legg-Calvé-Perthes disease (LCPD), an uncommon hip disorder affecting children aged 2-12 years.
Conference call for investors, analysts and the media

The Interim Report January – March 2024 will be presented by Medivir’s CEO, Jens Lindberg.

Time: Tuesday, April 30, 2024, at 10.00 (CET).

To access the webcast and find information about the teleconference, please click HERE!

The conference call will also be streamed via a link on the website: www.medivir.com/investors/calendar

The presentation will be available on Medivir’s website after completion of the conference.