On May 1, 2023 Erasca, Inc. (Nasdaq: ERAS), a clinical-stage precision oncology company singularly focused on discovering, developing, and commercializing therapies for patients with RAS/MAPK pathway-driven cancers, reported the United States Food and Drug Administration (FDA) has granted Fast Track Designation (FTD) to ERAS-801 for the treatment of adult patients with glioblastoma (GBM) with epidermal growth factor receptor (EGFR) gene alterations (Press release, Erasca, MAY 1, 2023, View Source [SID1234639356]). ERAS-801 is an orally bioavailable, small molecule EGFR inhibitor that exhibited substantial central nervous system (CNS) penetration in animal studies.

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FTD is designed to help drugs reach patients faster by facilitating the development and expediting the review of drugs with the potential to fill an unmet medical need by treating a serious or life-threatening condition. Programs that receive FTD benefit from early and frequent interactions with the FDA during the clinical development process and, if relevant criteria are met, the FDA may consider reviewing portions of a marketing application before the sponsor submits the complete application.

"Receiving FTD from the FDA underscores the serious unmet medical need in patients with GBM and reinforces the promise that ERAS-801 may offer as a differentiated treatment option," said Jonathan E. Lim, M.D., Erasca’s chairman, CEO, and co-founder. "GBM is an aggressive malignancy with high rates of relapse and a five-year survival rate below 10%. While over half of GBM cases are driven by EGFR alterations and/or amplifications, there are no approved EGFR inhibitors for the treatment of GBM due to the lack of sufficient brain penetration to treat primary brain tumors as well as lack of activity against EGFR alterations observed in GBM, such as EGFRvIII. To help overcome these limitations, ERAS-801 was specifically designed to have high CNS penetration and broad activity against both oncogenic and wildtype EGFR. We look forward to working closely with the FDA to expedite clinical development of ERAS-801 for these patients and anticipate reporting initial monotherapy data from the Phase 1 THUNDERBBOLT-1 trial in recurrent GBM (rGBM) in the second half of 2023."

ERAS-801 was designed and developed by a renowned team of cancer researchers—Michael Jung, Ph.D., Timothy Cloughesy, M.D., and David Nathanson, Ph.D.

About ERAS-801
ERAS-801 is a highly potent, selective, reversible, and orally available small molecule EGFR inhibitor with significantly enhanced CNS penetration. In animal models, ERAS-801 had a brain-to-plasma partition coefficient, Kp, of 3.7 and a corresponding unbound partition coefficient, Kp,uu, of 1.2, which was up to four times higher than approved EGFR inhibitors, suggesting that approximately 100% of the free drug in plasma is able to cross the blood-brain barrier (BBB). At clinically relevant exposures across 30 patient-derived GBM models that are intended to represent the heterogeneity of GBM, ERAS-801 demonstrated a survival benefit in 13 out of 14 (93%) EGFR mutant and/or amplified models and had statistically significantly higher brain penetrance and prolonged survival compared to approved EGFR tyrosine kinase inhibitors, including osimertinib, lapatinib, and erlotinib. ERAS-801 is currently being evaluated as a monotherapy in THUNDERBBOLT-1, an ongoing Phase 1 trial in patients with rGBM.

About THUNDERBBOLT-1
THUNDERBBOLT-1 is evaluating the safety, tolerability, and preliminary efficacy of ERAS-801 as a monotherapy in patients with rGBM. The dose escalation portion will determine the recommended dose, which will then be used during the dose expansion portion to further evaluate the efficacy and safety of ERAS-801. Future sub-studies of THUNDERBBOLT-1 may potentially explore ERAS-801 in combination with other agents and in broader patient types. Initial Phase 1 data from THUNDERBBOLT-1 are anticipated in the second half of 2023.

On May 1, 2023 Apple Tree Partners (ATP), a leader in life sciences venture capital, reported the launch of Initial Therapeutics, a biotechnology company created to make medicines that block notoriously difficult-to-drug protein targets with a new mode of action: selective termination of protein synthesis (STOPS) (Press release, Initial Therapeutics, MAY 1, 2023, View Source [SID1234632243]). Initial developed its proprietary STOPS platform to discover new therapeutics based on the recently demonstrated scientific premise that translation of a specific protein can be selectively interrupted at the moment in which its linear sequence is first produced in the exit tunnel of the ribosome.

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Initial was created by ATP with $75 million in Series A funding and co-founders Jamie H.D. Cate, Ph.D., Professor of Chemistry, Biochemistry, Biophysics, and Structural Biology at the University of California (UC) Berkeley; Brian Paegel, Ph.D., Professor of Pharmaceutical Sciences, Chemistry, and Biomedical Engineering at UC Irvine; and Kevan Shokat, Ph.D., Professor of Cellular and Molecular Pharmacology at UC San Francisco (UCSF) and Chemistry at UC Berkeley.

"Initial grew out of conversations between Jamie, Kevan, Brian, and me about work we had each been doing in these intersecting areas of protein synthesis kinetics, ribosome profiling, rapid chemistry, etc., and how we could collaborate to build something new to expand on the idea of selectively modulating protein translation, which we all saw as potentially transformative," said Spiros Liras, Ph.D., founding CEO of Initial Therapeutics and a venture partner at ATP. "The resulting combination of unmatched expertise and technologies brought by our founders grants Initial unique abilities to prosecute this new approach, and we are very excited about its promise to fight certain cancers and other serious illnesses."

Groundbreaking structural biology work from the Cate Lab has revealed how protein synthesis can be affected selectively in any phase of translation by interactions of small molecules with a complex that includes the ribosome and the nascent peptide chain of a target protein. Within Initial, this work has been industrialized with custom ribosomal assays scaled to ultra-large library screening using miniaturized microfluidics technology from the Paegel Lab.

"We started Initial Therapeutics to go after therapeutically important proteins that no one has been able to target successfully. I’m thrilled to see the amazing progress the Initial team has made on that front, with profound implications for the treatment of life-threatening diseases," Dr. Cate said.

Initial designs small molecule therapeutics to modulate the cellular synthesis of known, wellvalidated, high-value targets. Unlike interventions that work with mature proteins, such as targeted protein stabilization and protein degradation, Initial’s strategy circumvents the need to accommodate the cellular activity of the fully formed protein or to structurally solve for docking. Moreover, preventing protein synthesis may stave off aggregate formations and other diseaserelated molecular pathologies that are difficult to reverse, and in that regard Initial’s approach may offer therapeutic benefit. "Where other drug modalities involve recognition of the three-dimensional shape of the protein, Initial’s modality recognizes the primary linear sequence. I see that as a game-changer," said Dr. Shokat. "Some proteins don’t have ligandable pockets, but a linear sequence, that’s in everything. Initial’s bespoke platform allows us to go into the ribosome, the machinery of mRNA translation, in a selective way that has never before been technically possible." "When the therapeutic approach doesn’t concern mature proteins, the rules of drug discovery change and the universe of what is ‘druggable’ expands significantly," Dr. Paegel said.

On May 1, 2023, Century Therapeutics, Inc. (the "Company") reported a voluntary prepayment of all outstanding principal, accrued and unpaid interest, fees, costs and expenses, equal to $10.6 million in the aggregate (the "Payoff Amount"), under the Loan and Security Agreement (as amended, the "Loan Agreement"), dated as of September 14, 2020 between the Company and Hercules Capital, Inc. ("Hercules") (Filing, 8-K, Century Therapeutics, MAY 1, 2023, View Source [SID1234631085]). The Payoff Amount includes a prepayment charge of $100,000 equal to 1.0% of the outstanding principal, and an exit fee of $395,000. Upon receipt by Hercules of the Payoff Amount on May 1, 2023, all obligations, covenants, debts and liabilities of the Company under the Loan Agreement were satisfied and discharged in full, and the Loan Agreement and all other documents entered into in connection with the Loan Agreement were terminated.

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The Loan Agreement provided for a term loan with aggregate maximum borrowings of up to $30.0 million (the "Term Loan"). Under the Loan Agreement, the Company borrowed $10.0 million. The Term Loan bore interest at a variable annual rate equal to the greater of either (i) the sum of (a) 6.30% plus (b) the prime rate (as reported in the Wall Street Journal on the last business day of the month that immediately precedes the month in which the interest will accrue) or (ii) 9.55%. Interest-only payments on the borrowings under the Loan Agreement were due through May 1, 2023. After the interest-only payment period, borrowings under the Loan Agreement were due in equal monthly payments of principal and accrued interest until the maturity date of April 1, 2024.

On May 1, 2023, ImmunoGen, Inc. (the "Company") entered into an exchange agreement (the "Exchange Agreement") with RA Capital Healthcare Fund, L.P. (the "Shareholder") pursuant to which the Shareholder agreed to exchange 21,853,000 shares of the Company’s Common Stock, par value $.01 per share (the "Common Stock"), for 21,853 shares of newly designated Series A Convertible Preferred Stock, par value $.01 per share (the "Preferred Stock") (the "Exchange") (Filing, 8-K, ImmunoGen, MAY 1, 2023, View Source [SID1234630841]). The preferences, rights, and limitations of the Preferred Stock are set forth in a Certificate of Designation (the "Certificate of Designation") attached to the Exchange Agreement. In connection with the Exchange, on May 2, 2023, the Company filed Articles of Amendment to the Company’s Articles of Organization, as amended, which included the Certificate of Designation, with the Secretary of the Commonwealth of Massachusetts.

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Each share of the Preferred Stock is convertible into 1,000 shares of Common Stock at the option of the holder at any time until the tenth anniversary of the issuance of the Preferred Stock, at which time the Preferred Stock will automatically convert to Common Stock. In addition, the Company has the right to request the conversion of the Preferred Stock into Common Stock in certain circumstances. The conversion of the Preferred Stock into Common Stock is subject to certain limitations, including that the holder will be prohibited from converting the Preferred Stock into Common Stock if, as a result of such conversion, the holder (together with its affiliates and any other persons whose beneficial ownership of Common Stock would be aggregated with the holder for purposes of Section 13(d) of the Securities Exchange Act of 1934, as amended) would beneficially own a number of shares of Common Stock above a conversion blocker (the "Conversion Blocker"), which is initially set at 9.99% of the total Common Stock then issued and outstanding immediately following the conversion of such shares of Preferred Stock. Holders of the Preferred Stock are permitted to increase or decrease the Conversion Blocker to an amount not to exceed 19.99% upon 61 days’ prior notice from the holder to the Company.

Shares of the Preferred Stock will have no voting rights, except as required by law and except that the affirmative vote of the holders of the then outstanding Preferred Stock will be required to amend the terms of the Preferred Stock, increase the number of authorized shares of Preferred Stock or enter into an agreement with respect to any of the foregoing. The holders of the Preferred Stock are entitled to receive a nominal preference of $0.001 per share of Preferred Stock upon the liquidation, dissolution, or winding up of the Company (the "Liquidation Preference") before any payments are made or any assets are distributed to holders of the Common Stock. However, if the amount payable to holders of the Common Stock upon the Company’s liquidation, dissolution, or winding up is greater than the Liquidation Preference on a per share basis, then the holders of the Preferred Stock will instead receive, on a per-share and as-converted basis, the same assets that are distributed to holders of the Common Stock. In the event of certain fundamental transactions, including a merger, holders of the Preferred Stock will automatically receive, as consideration for the Preferred Stock, the same kind and amount of securities, cash, or property as the holders of the Preferred Stock would have been entitled to receive had the holders of the Preferred Stock instead held Common Stock immediately prior to the occurrence of the fundamental transaction, subject to certain exceptions.

The Exchange is expected to close on or around May 3, 2023. The Preferred Stock will be issued without registration under the Securities Act of 1933, as amended (the "Securities Act"), in reliance on the exemption from registration contained in Section 3(a)(9) of the Securities Act.

The foregoing description of the Preferred Stock and the Exchange Agreement is not complete and is qualified in its entirety by reference to the full text of the Articles of Amendment, which includes the Certificate of Designation, and the Exchange Agreement, which are filed as Exhibits 3.1 and 10.1 to this Current Report on Form 8-K and are incorporated by reference herein.

On May 1, 2023 Marker Therapeutics, Inc, a clinical-stage company specializing in the development of next-generation T cell-based immunotherapies for the treatment of hematological malignancies and solid tumor indications, reported that it has entered into a comprehensive agreement with CellReady, a newly formed Contract Development and Manufacturing Organization (CDMO) founded by John Wilson, founder and CEO of Wilson Wolf Corporation and Marker Co-Founder and Board Member (Filing, Marker Therapeutics, MAY 1, 2023, View Source [SID1234630805]).

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Under the terms of the non-dilutive agreement, CellReady will purchase certain cell manufacturing assets from Marker for approximately $19 million in cash and reduce Marker’s overhead by about $11 million annually by employing Marker’s manufacturing, development, quality, and regulatory affairs personnel, and assuming the leases for Marker’s Houston-based manufacturing and research and development facilities. The parties anticipate the transaction will close on June 26, 2023.

CellReady also agreed to enter into a long-term contract with Marker wherein CellReady will perform a wide variety of services for Marker including research and development, manufacturing, and regulatory activity in support of Marker’s clinical trials.

This agreement allows Marker to concentrate solely on the clinical advancement of its unique form of T cell therapy, which has demonstrated the ability to recognize and kill cancer cells even as the cancer cells evolve to escape detection. Currently approved genetically engineered CAR T and TCR therapies cannot recognize evolving cancer cells, and this limitation can lead to relapse.

Juan Vera, M.D., formerly Marker’s COO and Chief Scientific Officer, has assumed the role of Chief Executive Officer of Marker Therapeutics effective May 1, 2023. Dr. Vera commented, "Marker’s management and impartial members of the board worked with John Wilson and CellReady to develop a very creative and non-dilutive plan that provides Marker with the financial runway to pursue its clinical priorities through the end of 2025. At the same time, through CellReady, Marker will maintain full access to its industry-leading operational, quality, development, and regulatory team and facilities whenever it needs them. I look forward to working with the Marker clinical team to advance the development of MT-601 in our ongoing non-Hodgkin’s lymphoma trial and eventual pancreatic cancer trial, in addition to MT-401 for our post-transplant AML trail. Additionally, I am spearheading a strategic review process of our clinical programs with the Marker management team as part of our restructuring efforts."

Mr. John Wilson, founder and CEO of Wilson Wolf Corporation and Marker Co-Founder and Board Member, stated, "I continue to believe that Marker’s unique therapies can make a positive impact in the cancer field. This is why I co-founded Marker, made investments along the way, and have remained a longtime shareholder. Advancing these therapies would not be possible without the institutional and retail investors who have joined our mission. The reality is that Marker has not yet met our investors’ expectations. Therefore, extending Marker’s clinical runway without investor dilution is the right thing to do. Paying Marker approximately $19 million in cash and simultaneously eliminating about $11 million of Marker’s annual costs related to its personnel and facilities, greatly reduces Marker’s cash needs as it pursues clinical development of its lead programs. Meanwhile, CellReady will provide Marker with all resources required to advance its clinical program, including people, facilities, and cell manufacturing capabilities. I estimate the net benefit to Marker to be approximately $42 million through the end of 2025."

Marker’s Clinical Strategy Update
Marker’s MT-601, a multi-tumor-associated antigen (multi-TAA) specific T cell product targeting six cancer antigens, is in an ongoing clinical trial for the treatment of patients with relapsed/refractory non-Hodgkin’s lymphoma who have failed, or are ineligible to receive, an anti-CD19 CAR T cell treatment.

The MT-601 study is based on the results that were observed in the Phase I/II TACTAL study that enrolled patients with Hodgkin’s and non-Hodgkin’s lymphoma. The TACTAL study, which used a multi-TAA specific T cell product targeting five lymphoma antigens, reported long-term complete response (CR) rates that were comparable to recently approved anti-CD19 CAR-T cell therapies, even at very low cell doses.

Marker is also continuing the clinical development of MT-401, its multi-TAA specific T cell product for the treatment of pediatric and adult patients with acute myeloid leukemia (AML) after receiving allogeneic transplant. AML is a very challenging form of cancer and, in September 2022, Marker indicated that it had observed promising early clinical results which suggested that MT-401 can potentially rescue post-transplant AML patients with measurable residual disease. Should data continue to demonstrate the potential to stop AML from progressing into the dire condition of Frank Relapse, Marker believes this will be a significant advance in AML treatment.

Through extensive scientific review, Marker believes the magnitude of a patient’s tumor burden may correlate with MT-401 and MT-601 clinical outcomes. Marker is now updating clinical protocols to potentially improve patient outcomes by assessing tumor burden. Data availability is expected toward the latter half of 2024.

Marker’s pancreatic trial is awaiting news on grant funding and Marker is analyzing the relationship between starting cellular material and manufactured cell quantity to ensure optimal conditions for its pancreatic trial outcomes. Marker will be following up to keep investors informed about the status of its pancreatic trial as information becomes available.

Key Transaction Terms

In connection with this transaction, Marker’s board of directors established a special transactions committee of impartial directors to review the terms of the transaction, as well as other strategic alternatives, and to issue a recommendation to the board of directors. The impartial members of the board of directors unanimously approved entry into the transaction based on the special transactions committee’s recommendation.

Pursuant to the agreement, Marker has made certain representations and warranties on the transferred assets and has agreed to certain customary covenants and restrictions with respect to assets and liabilities comprising the transaction consistent with a transaction of this nature.

The parties will also enter into a long-term supply agreement for the manufacture and supply of Marker’s clinical product candidates.