On April 30, 2024, bluebird bio, Inc. (the "Company") entered into an amendment (the "Amendment") to its Loan and Security Agreement (the "LSA"), dated as of March 15, 2024, by and among the Company, the several banks and other financial institutions or entities party thereto, as lenders (collectively, the "Lenders"), and Hercules Capital, Inc., as administrative agent and collateral agent (the "Agent") (Filing, 8-K, bluebird bio, APR 30, 2024, View Source [SID1234642629]). The Amendment relates to certain provisions of the LSA that are affected by the Company’s previously announced plan to restate its consolidated financial statements as of and for the year ended December 31, 2022 and unaudited financial information for each of the first three quarters of 2023 and 2022 in its Annual Report on Form 10-K for the year ended December 31, 2023 (the "2023 Form 10-K"). The work required to complete all necessary procedures in connection with the restatements has resulted in a delay in filing the 2023 Form 10-K and is anticipated to result in a delay in filing the Company’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2024 (the "Q1 Form 10-Q").

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Pursuant to the Amendment, the Company, the Agent and the Lenders agreed to, among other things: (i) revised monthly financial reporting metrics required to be provided by the Company to the Lenders for each of the months ending March 31, 2024 through June 30, 2024; and (ii) extension of the deadlines by which the Company must provide to the Lenders financial statements for the year ended December 31, 2023 and for the quarter ended March 31, 2024. Further, the Amendment provides that the Company’s late delivery and filing of the 2023 Form 10-K and the Q1 Form 10-Q shall not be deemed a violation of the Company’s covenant to maintain compliance with applicable law, so long as such documents are filed by the extended deadlines.

The foregoing description of the Amendment does not purport to be complete and is qualified in its entirety by the full text of the LSA and the Amendment, copies of which are filed as Exhibits 10.1 and 10.2 to this Current Report on Form 8-K and incorporated herein by reference.

On April 30, 2024 Imugene Limited (ASX:IMU), a clinical-stage immuno‐ oncology company, reported its Quarterly Cash Flow report (Appendix 4C) for the quarter ended 31 March 2024 (Press release, Imugene, APR 30, 2024, View Source [SID1234642537]).

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On April 30, 2024 ALX Oncology Holdings Inc., ("ALX Oncology" or "the Company") (Nasdaq: ALXO), an immuno-oncology company developing therapies that block the CD47 immune checkpoint pathway, reported the initiation of a Phase 2 investigator-sponsored trial ("IST") of neoadjuvant radiation and evorpacept, a next-generation CD47 blocker, in combination KEYTRUDA (pembrolizumab) in patients with previously untreated and early-stage locally advanced, resectable, human papillomavirus-mediated oropharyngeal cancer ("HPVOC") (Press release, ALX Oncology, APR 30, 2024, View Source [SID1234642505]). This multi-center, single-arm, open-label Phase 2 IST is being led by Joseph A. Califano III, M.D., Director of the Hanna and Mark Gleiberman Head and Neck Cancer Center at the University of California, San Diego (NCT05787639).

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"Despite standard immune and chemoradiation neoadjuvant therapies for patients with locoregionally advanced HPVOC, associated severe toxicities and lack of durable responses underscore the need for novel therapies" said Dr. Califano. "Early clinical studies with immunotherapy in combination with stereotactic body radiation therapy, which precisely delivers high doses of radiation to a small target, have shown encouraging immune-mediated anti-tumor responses in these patients. Radiotherapy induces the release of tumor-associated antigens and upregulates PD-L1 expression by tumor cells. Blocking the CD47/SIRPα axis may yield a synergistic anti-tumor effect when combined with radiotherapy and immunotherapy. The addition of evorpacept to neoadjuvant immunoradiotherapy is a promising concept that could be an effective new strategy to downstage patients prior to surgery."

About Oropharyngeal Cancer

Approximately 58,000 people in the U.S. are diagnosed with pharyngeal and oral cavity cancers, a form of HNSCC, each year.1 The most frequently cited risk factors for these cancers are tobacco and alcohol use. More recently, epidemiologic and experimental data have reported increased rates of HPV being present upon a patient receiving diagnosis of oropharyngeal cancer. Standard treatment options for intermediate risk HPVOPC include 7 weeks of definitive chemoradiation, or surgery plus 6 weeks of risk adapted adjuvant radiation +/- chemotherapy. Despite advances in treatment, 5-year survival for localized disease is 88% and declines to 38% for metastatic disease.1

On April 30, 2024 Enlaza Therapeutics, the first covalent biologic platform company, reported a $100 million Series A financing (Press release, Enlaza Therapeutics, APR 30, 2024, View Source [SID1234642490]). The financing will be used to further develop Enlaza’s proprietary covalent protein technologies and to support advancement of wholly owned pipeline programs to the clinic.

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The financing was led by the Life Sciences group of J.P. Morgan Asset Management’s Private Capital division, with participation from existing investors: Frazier Life Sciences, Avalon Ventures, Lightspeed Venture Partners, and Samsara BioCapital. The financing also includes new investors: Amgen Ventures, Regeneron Ventures, Bregua Corporation, Pappas Capital, and Alexandria Venture Investments. Concurrent with the financing, Stephen Squinto, Ph.D., Chief Investment Officer (CIO) of the Life Sciences group of J.P. Morgan Private Capital, was named to the Board of Directors.

"We are thrilled to close this financing with a group of new and existing investors that share our vision of creating a novel, differentiated class of protein therapeutics in oncology and other therapeutic areas," said Sergio Duron, Ph.D., CEO of Enlaza Therapeutics. "This support will enable continued expansion of our covalent protein drug platform, establishment of a diversified pipeline that demonstrates the broad potential of this approach, and advancement of our lead assets toward clinical development."

"Bringing covalency to the biologics market is an extremely valuable way to unlock the next generation of protein therapeutics that are safer and more tolerable and can be dosed more frequently with lower doses," said Stephen Squinto, CIO of Life Sciences group of J.P. Morgan Private Capital. "We believe Enlaza’s platform is well positioned for many first-in-class and best-in-class opportunities and are excited to partner with this senior management team."

Enlaza’s covalent biologic platform, called War-LockTM, creates highly specific therapeutic warheads that covalently bind to drug targets of interest. This white-space technology enables, for the first time, a covalent-acting protein drug that retains the selectivity of small-format biologics. These unique protein drugs enable specific covalent binding to an intended protein target, improving efficacy while simultaneously reducing toxicities related to sustained peripheral exposure.

The War-Lock platform has broad applications and produces therapeutic candidates with excellent drug-like properties. Protein drugs produced by the platform can be modified to incorporate various payloads and achieve specific delivery to target tissues with high fidelity. Enlaza has generated further preclinical data for its oncology drug candidates supporting the covalent mechanism of action by demonstrating efficient tumor penetration coupled with rapid systemic clearance, high tumor retention, and low off-target liabilities. These data have enabled Enlaza to develop a high-value pipeline of covalent protein drugs.

The company’s Board of Directors is comprised of Stephen Squinto, Ph.D., J.P. Morgan Private Capital; Jamie Topper, M.D., Ph.D., Frazier Life Sciences, Jay Lichter, Ph.D., Avalon Ventures; Shelley Chu, M.D., Ph.D., Lightspeed Venture Partners; Marcos Milla, Ph.D., Samsara BioCapital, and Sergio Duron, Ph.D., CEO, Enlaza Therapeutics.

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.