University of Tsukuba and Astellas Confirm a Strategic Partnership

On November 16, 2023 University of Tsukuba (President: Kyosuke Nagata) and Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura, "Astellas") reported that they have signed a letter of confirmation regarding a strategic partnership to accelerate the digitalization of the drug discovery research field, as well as the development of the life science ecosystem in Tsukuba and Kashiwa-no-ha, and to further accelerate innovative drug discovery research and development (Press release, Astellas, NOV 16, 2023, View Source [SID1234637732]).

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!

Under this agreement, the two parties will exchange information on and discuss:
Promotion of drug discovery and other research, and creation of new startups through industry-academia collaboration between the two parties
Utilization of cutting-edge research equipment, drug discovery-related data and research seeds mutually owned by the two parties
Implementation of discussions and seminars to accelerate and develop collaborative research already conducted by the two parties
Promotion of drug discovery research and creation of new startups through exchange and communication with third-party venture company innovators in residence at SakuLabTM-Tsukuba*1
Based on this agreement, the University of Tsukuba will establish an office in Astellas’ SakuLabTM-Tsukuba for the Tsukuba Digital-Bio International Center*2, where they are participating as a lead organization. The center will provide an environment where researchers from different fields including researchers specializing in medicine, biotechnology, and the AI/digital analytics field from the University of Tsukuba and Astellas’ researchers specializing in drug discovery can discuss freely and energetically, aiming to create a place for innovative and active co-creative research through the fusion of different fields.

Hiroyuki Nishiyama, M.D., Ph.D., Leader of Tsukuba Digital-Bio International Center
"In western drug discovery ecosystems, researchers and innovators have quick and easy access to cutting-edge research results and trends in their fields of expertise. Japanese pharmaceutical companies tend to look there because they can’t obtain enough information in Japanese drug discovery ecosystems. Against this background, we have been discussing with Astellas for the past one and a half years to change the conventional frame of reference. I believe that we can flexibly and speedily formulate new joint research themes not limited to specific fields and execute efficient research by sharing our research information (seeds) and areas of research interest at Astellas. We will work to build a drug discovery ecosystem in Japan that will enable start-ups to be implemented in society. We hope that this initiative will be one opportunity to overcome the barrier known as the "valley of death" that exists when translating academia research results into social implementations."

Yoshitsugu Shitaka, Ph.D., Chief Scientific Officer (CScO) of Astellas
"We are very pleased to confirm this strategic partnership with the University of Tsukuba, the flagship university of Tsukuba Science City. We believe our scope of knowledge and experience in drug research, and our global network will pair well with the University of Tsukuba’s outstanding expertise in medicine, biotechnology, and the AI/digital field. Together we aim for further growth in the life science ecosystem in Tsukuba and the Kashiwa-no-ha areas, with SakuLabTM-Tsukuba as a starting point for innovation. We envision the collaboration will enable visionary ideas and specialized knowledge to converge, turbocharging the development of pioneering healthcare solutions."

Astellas has already reflected the impact from this agreement in its financial forecast of the current fiscal year ending March 31, 2024.

Alpha Tau Medical Announces Third Quarter 2023 Financial Results and Provides Corporate Update

On November 16, 2023 Alpha Tau Medical Ltd. ("Alpha Tau", or the "Company") (NASDAQ: DRTS, DRTSW), the developer of the innovative alpha-radiation cancer therapy Alpha DaRT, reported third quarter 2023 financial results and provided a corporate update (Press release, Alpha Tau Medical, NOV 16, 2023, View Source [SID1234637731]).

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!

"This year has already seen tremendous progress, as we advance our ReSTART pivotal U.S. multi-center trial in recurrent cutaneous squamous cell carcinoma, which is expected to produce data in 2024, and continue to initiate a series of feasibility trials in difficult-to-treat internal organ tumors with high unmet need, such as pancreatic and liver cancers," stated Alpha Tau CEO Uzi Sofer. "We are looking forward to meaningful inflection points during the rest of 2023, including interim safety and feasibility data from our pancreatic cancer trial in Montreal, and our forthcoming submission in Japan for pre-market approval. In parallel, we are preparing for future product launches by advancing our commercial planning activities and solidifying our supply chain, which was recently bolstered by a valuable land grant in Jerusalem that is expected to increase our future manufacturing capacity as well as the leasing of a second manufacturing site in the U.S. Alpha Tau remains adequately capitalized to support all of these programs over the coming years," he concluded.

Recent Corporate Highlights:

● In October, the Company announced that it had entered into a long-term lease agreement for a standalone building of over 14,000 rentable square feet in Hudson, NH, with the intention of erecting the Company’s second U.S. manufacturing site, alongside its first site in nearby Lawrence, MA.

● In October, the Company announced that Dr. Stephen Hahn, a former commissioner of the U.S. Food and Drug Administration (FDA) and a distinguished expert in the field of radiation oncology and translational clinical research, has joined its Scientific Advisory Board.

● In September, the first patient with advanced inoperable pancreatic cancer was treated with Alpha DaRT at Hadassah Medical in Jerusalem, Israel, in parallel to the Company’s ongoing safety and feasibility trial for the treatment of advanced inoperable pancreatic cancer currently underway in Montreal, Canada.

● In August, Alpha Tau reported long-term safety and tumor control outcomes data for patients with unresectable, recurrent, or locally advanced head and neck or skin tumors treated with Alpha DaRT across four prospective trials conducted at several international institutions. In this analysis, 81 lesions were treated in 71 patients. The median follow-up was 14 months (range: 2-51 months). A complete response (CR) was observed in 89% of treated lesions (n=72), 10% (n=8) demonstrated a partial response, and one patient was not evaluable. The two-year actuarial local recurrence-free survival (LRFS) rate was 77% [95% CI: 63–87%]. Twenty percent of patients developed treatment-related acute grade 2 toxicity (such as dermatitis radiation, local pain at the treatment site or pruritus), which subsequently resolved with conservative treatment; there were no grade 3 or higher related acute toxicities reported. There were no grade 2 or higher ‘late toxicities’, defined as toxicities occurring six months after Alpha DaRT treatment or later, observed in this cohort.

Upcoming Near-Term Milestones

● Expecting to release interim safety and feasibility data in Q4 2023 from the first five patients treated in the Company’s study examining the use of Alpha DaRT to treat patients in Montreal, Canada with advanced inoperable pancreatic cancer. For more information please see here: View Source

● Expecting to submit to the PMDA in Japan in Q4 2023 for pre-market approval for Alpha DaRT in patients with recurrent head & neck cancer.

● Planning treatment of the first patient in the Canadian liver metastases safety and feasibility trial in Q4 2023 or Q1 2024. The trial is currently open for recruitment; for more information please see here: View Source

● Planning treatment of the first patient in the Israeli recurrent lung cancer safety and feasibility trial in H1 2024. The trial is currently open for recruitment; for more information please see here: View Source

● Targeting first brain cancer treatment in H1 2024.

● Targeting completion of patient recruitment in the ReSTART pivotal U.S. multi-center trial in recurrent cutaneous squamous cell carcinoma in Q2 2024. For more information please see here: View Source

Financial results for nine months ended September 30, 2023

R&D expenses for the nine months ended September 30, 2023 were $18.9 million, compared to $15.5 million for the same period in 2022, due to increased employee compensation and benefits, including share-based compensation, increased pre-clinical study and clinical trial expenses particularly in our U.S. multi-center pivotal trial, and reduced government grants, offset by lower expenses in Japan because of the completion of our clinical study in Japan last year.

Marketing expenses for the nine months ended September 30, 2023 were $1.5 million, compared to $0.6 million for the same period in 2022, due to increased employee compensation and benefits, including share-based compensation for marketing personnel including our chief commercial officer hired in 2022, as well as increased marketing activities.

G&A expenses for the nine months ended September 30, 2023 were $5.3 million, compared to $8.1 million for the same period in 2022, due to decreased compensation expenses as well as one-time expenses in 2022 associated with the Company’s merger with Healthcare Capital Corp.

Financial income, net, for the nine months ended September 30, 2023 was $4.0 million, compared to financial expense, net of $6.2 million, for the same period in 2022, due to a decrease in remeasurement of warrants, an increase in interest from bank deposits, and changes in foreign exchange rates.

For the nine months ended September 30, 2023, the Company had a net loss of $21.8 million, or $0.31 per share, compared to a net loss of $30.4 million, or $0.49 per share, in the same period of 2022.

Balance Sheet Highlights

As of September 30, 2023, the Company had cash, restricted cash, deposits and restricted deposits in the amount of $90.1 million, compared to $105.4 million on December 31, 2022. The Company expects that this cash balance will be sufficient to fund operations for at least two years.

Alentis Therapeutics Doses First Patient in Phase 1/2 Clinical Trial of ALE.C04 in Head and Neck Squamous Cell Carcinoma (HNSCC)

On November 16, 2023 Alentis Therapeutics ("Alentis"), a clinical-stage biotechnology company developing treatments for Claudin-1 positive (CLDN1+) tumors and organ fibrosis, reported that the first patient has been dosed in a Phase 1/2 clinical trial of ALE.C04, a Claudin-1 (CLDN1) targeting investigational antibody for the treatment of CLDN1+ tumors (Press release, Alentis Therapeutics, NOV 16, 2023, View Source [SID1234637725]). The patient is enrolled under the Phase I program, led by Anthony El-Khoueiry, MD, Associate Director of Clinical Research, at University of Southern California (USC) Norris Comprehensive Cancer Center, part of Keck Medicine of USC.

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 open-label, multi-center, Phase 1/2 clinical trial (NCT06054477) will investigate ALE.C04 as a single agent and in combination with pembrolizumab (anti-PD-1 antibody) in 220 adults with recurrent or metastatic (R/M) head and neck squamous cell carcinoma. Endpoints include safety, tolerability, pharmacokinetics and anti-tumor efficacy.

"ALE.C04 is a first-in-class antibody for treating cancer and has shown much potential in preclinical models," said Luigi Manenti, MD, Chief Medical Officer of Alentis. "ALE.C04 is designed to kill CLDN1+ tumor cells directly and to break the check-point inhibitor treatment resistance by restoring immune cell trafficking."

Jacob Thomas, MD, principal investigator on the trial at USC Norris and Assistant Professor of Medicine at Keck School of Medicine of USC added, "Patients with R/M HNSCC have poor outcomes, and novel effective therapies are needed in this setting. The mechanism of action and preclinical data for ALE.C04 provide sound scientific rationale for its evaluation in HNSCC."

Prof. Josep Tabernero, Head of Medical Oncology at Vall d’Hebron University Hospital said, "This first-in-human trial will provide valuable information on ALE.C04 as a monotherapy and in combination with anti-PD-1 treatment. I am looking forward to the data and to developing ALE.C04 for other CLDN1+ tumors including colorectal cancer."

About ALE.C04
ALE.C04 is a first-in-class monoclonal antibody developed to specifically target exposed CLDN1 on cancer cells. This investigational antibody is designed to treat cancer in two ways: remodeling of the extracellular matrix, leading to improved NK and T-cell trafficking and direct tumor cell killing through the effector function. This unique mechanism of action provides ALE.C04 with therapeutic potential as a monotherapy and in combination. ALE.C04 received Fast Track designation from the Food and Drug Administration for the treatment of CLDN1+ HNSCC.

About HNSCC
Head and neck squamous cell carcinoma, or HNSCC, is the 6th most common cancer worldwide and because the number of cases is quickly rising, safer and more effective treatments are urgently needed. Despite advances in treatment, the 5-year survival rate remains at about 57%.

Entry into a Material Definitive Agreement

On November 15, 2023, Alkermes plc (the "Company") reported the previously announced separation of its oncology business into Mural Oncology plc ("Mural"), a new, independent, publicly-traded company (the "Separation") (Filing, Alkermes, NOV 15, 2023, View Source [SID1234639963]). The Separation was effected by means of a distribution of all of the outstanding ordinary shares of Mural to the Company’s shareholders (the "Distribution"), in which each of the Company’s shareholders received one ordinary share, nominal value $0.01 per share, of Mural for every ten ordinary shares, par value $0.01 per share, of the Company (the "Distribution Ratio") held by such shareholder as of the close of business on November 6, 2023, the record date for the Distribution (the "Record Date"). The effective time of the Distribution was 12:01 a.m. Eastern time on November 15, 2023.

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!

Separation Agreement

In connection with the Separation, the Company entered into a separation agreement with Mural, dated as of November 13, 2023, that, among other things, sets forth the Company’s agreements with Mural regarding the principal actions to be taken in connection with the Separation, including the Distribution. The separation agreement identifies assets to be transferred to, liabilities to be assumed by and contracts to be assigned to Mural, including the operating lease for 850 and 852 Winter Street in Waltham, Massachusetts, as part of the Separation, and it provides for when and how such transfers, assumptions and assignments occur. The purpose of the separation agreement is to provide Mural and the Company with those assets necessary to operate their respective businesses and to retain or assume the respective liabilities related to those assets. Under the terms of the separation agreement, the Company granted Mural a perpetual, worldwide, non-exclusive, royalty-free, fully paid-up license (or, as the case may be, sublicense) to intellectual property controlled by the Company as of the date of the Distribution to allow Mural to use such intellectual property for the oncology business, and Mural granted the Company a perpetual, worldwide, non-exclusive, royalty-free, fully paid-up license (or, as the case may be, sublicense) to intellectual property transferred to Mural as part of the Separation for the Company’s use outside of the oncology business. Each of Mural and the Company agreed to releases with respect to pre-Distribution claims, and cross-indemnities with respect to post-Distribution claims, that are principally designed to place financial responsibility for the obligations and liabilities allocated to Mural under the separation agreement with Mural, and financial responsibility for the obligations and liabilities allocated to the Company under the separation agreement with the Company. The Company and Mural are also each subject to mutual six-month employee non-solicitation and non-hire restrictions, subject to certain customary exceptions, and certain confidentiality restrictions and information sharing obligations.

Tax Matters Agreement

In connection with the Separation, the Company also entered into a tax matters agreement with Mural, dated as of November 13, 2023. The tax matters agreement governs the Company’s and Mural’s respective rights, responsibilities and obligations with respect to taxes (including taxes arising in the ordinary course of business and taxes, if any, incurred as a result of any failure of the Distribution, together with certain related transactions, to qualify as tax-free for U.S. federal income tax purposes), tax attributes, the preparation and filing of tax returns, the control of audits and other tax proceedings, and assistance and cooperation in respect of tax matters.

In addition, the tax matters agreement imposes certain restrictions on Mural and its subsidiaries (including restrictions on share issuances, business combinations, sales of assets and similar transactions) and on the Company and its subsidiaries that are designed to prevent the taking of any actions that would adversely affect, or could reasonably be expected to adversely affect, the tax-free status of the Distribution, together with certain related transactions. The tax matters agreement provides special rules that allocate tax liabilities in the event that the Distribution, together with certain related transactions, is not tax-free. In general, under the terms of the tax matters agreement, if the Distribution, together with certain related transactions, were to fail to qualify as a transaction that is tax-free for U.S. federal income tax purposes, under Sections 355 and 368(a)(1)(D) of the Internal Revenue Code of 1986, as amended (the "Code"), and if and to the extent that such failure results from certain actions, omissions or failures to act by the Company, including a prohibited change of control in the Company under Section 355(e) of the Code or an acquisition of shares or assets of the Company, then the Company will bear any resulting taxes, interest, penalties and other costs. If and to the extent that such failure results from certain actions, omissions or failures to act by Mural, including a prohibited change of control in Mural under Section 355(e) of the Code or an acquisition of shares or assets of Mural, then Mural will indemnify the Company for any resulting taxes, interest, penalties and other costs. If such failure does not result from a prohibited change of control in the Company or Mural under Section 355(e) of the Code and both the Company and Mural are responsible for such failure, liability will be shared according to relative fault. If neither Mural nor the Company is responsible for such failure, the Company will bear any resulting taxes, interest, penalties and other costs.

Employee Matters Agreement

In connection with the Separation, the Company also entered into an employee matters agreement with Mural, dated as of November 13, 2023. The employee matters agreement governs the Company’s, Mural’s and their respective subsidiaries’ and affiliates’ rights, responsibilities and obligations after the Separation with respect to, employment, benefits and compensation matters relating to employees and former employees (and their respective dependents and beneficiaries) who are or were associated with the Company, including those who became employees of Mural in connection with the Separation; the allocation of assets and liabilities generally relating to employees, employment or service-related matters and employee benefit plans; other human resources, employment and employee benefits matters; and the treatment of equity-based awards granted by the Company prior to the Separation.

Transition Services Agreements

Alkermes, Inc., a wholly-owned subsidiary of the Company ("Company Subsidiary"), and Mural Oncology, Inc., a wholly-owned subsidiary of Mural ("Mural Subsidiary"), entered into a transition services agreement on November 13, 2023, pursuant to which the Company and its subsidiaries will provide, on an interim, transitional basis, various services to Mural and its subsidiaries, including services related to corporate functions such as finance, human resources, internal audit, research and development, financial reporting, and information technology, each for a term of two years, unless earlier terminated in accordance with the terms of such agreement.

Company Subsidiary and Mural Subsidiary also entered into a second transition services agreement on November 13, 2023, pursuant to which Mural and its subsidiaries will provide certain services to the Company and its subsidiaries, each for a term of two years, unless earlier terminated in accordance with the terms of such agreement.

The foregoing descriptions of the separation agreement, the tax matters agreement, the employee matters agreement, and the transition services agreements do not purport to be complete, provide only summaries of the material terms of such agreements and are qualified in their entirety by reference to each of the agreements, which are filed as Exhibit 2.1, Exhibit 10.1, Exhibit 10.2, Exhibit 10.3, and Exhibit 10.4, respectively, to this Current Report on Form 8-K and are incorporated herein by reference.

Mural Oncology Launches to Advance Pipeline of Novel Engineered Cytokine Immunotherapies

On November 20, 2023 Mural Oncology plc (Nasdaq: MURA) reported to have launched as an independent, publicly traded, clinical-stage immuno-oncology company leveraging its core competencies in immune cell modulation and protein engineering to develop novel, investigational engineered cytokine therapies designed to address areas of unmet need for patients with a variety of cancers (Press release, Mural Oncology, NOV 15, 2023, View Source [SID1234637844]). Mural’s ordinary shares will begin trading on the Nasdaq Global Market tomorrow, November 16th, under the ticker symbol "MURA".

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!

"Immunotherapies have made a tremendous impact on the treatment of cancers over the past decade," said Caroline Loew, Ph.D., the Company’s chief executive officer. "Unfortunately, many patients either do not respond or do not have durable responses. We believe Mural Oncology can lead the future of immunotherapies for patients. Our protein engineering expertise allows us to reimagine the development of pro-inflammatory cytokine-based therapeutics that could address the key limitations with current cancer immunotherapies. I am thrilled to lead this company and am energized by the enormous potential of our lead clinical candidate, our preclinical programs, and our underlying protein engineering capabilities."

Mural Oncology’s pipeline is built to address difficult-to-treat tumor types where checkpoint inhibitors are not effective. The Company’s lead product candidate, nemvaleukin alfa (nemvaleukin), is an investigational, engineered interleukin-2 (IL-2) cytokine designed to capture and expand the therapeutic benefits of high-dose recombinant human IL-2 (rhIL-2), while mitigating the hallmark toxicities of native IL-2 in difficult-to-treat cancers with high unmet need. Nemvaleukin is currently in two potentially registrational studies: one for the treatment of mucosal melanoma as a monotherapy and one for the treatment of platinum-resistant ovarian cancer (PROC) in combination with pembrolizumab.

In addition to nemvaleukin, Mural Oncology has discovery-stage programs in IL-18 and IL-12, focused on proinflammatory cytokines that leverage the Company’s immune cell modulation expertise and protein engineering capabilities. This multi-faceted approach to cytokine engineering is aimed at maximizing the utility of identified cytokines and includes binding selectivity, tumor-targeting, half-life modification, and stable fusion proteins.

"We believe nemvaleukin has the potential to reduce native IL-2’s toxicities, potentially allowing greater tolerability and efficacy than other IL-2 molecules have shown in the past," Dr. Loew continued. "We plan to report top-line results in each of mucosal melanoma and PROC in the first quarter of 2025 and declare product candidates across both of our other discovery-stage programs in 2024. We are building on years of foundational work from which our engineered cytokines may lead to new therapies for significant patient populations where checkpoint inhibitors either failed to achieve a response or produced a limited response. We believe these new therapies could be effective either as monotherapies or in combination with a range of other therapeutics."

To advance the Company’s pipeline and capitalize on its protein engineering capabilities, Mural has assembled an experienced and highly accomplished executive team and board of directors.

Mural Oncology’s executive officers:

Caroline Loew, Ph.D., chief executive officer, was previously president and chief executive officer of Glympse Bio. Prior to Glympse, she was vice president, head of R&D strategy and planning at Bristol-Myers Squibb (BMS). Dr. Loew joined BMS following leadership roles at Merck and PhRMA, where she led teams responsible for commercial portfolio management, market access, and regulatory policy.
Adam Cutler, chief financial officer, was previously chief financial officer of both Q32 Bio and Molecular Templates. Prior to that, he was senior vice president of corporate affairs at Arbutus Biopharma.
Vicki Goodman, M.D., chief medical officer, was previously executive vice president, product development & medical affairs, and chief medical officer of Exelixis. Previously, she was vice president, clinical research and therapeutic area head, late-stage oncology at Merck where she oversaw the company’s late-stage development portfolio, including pembrolizumab. Prior to Merck, she was a member of BMS’s oncology senior leadership team, managing a team developing nivolumab and ipilimumab.
Maiken Keson-Brookes, chief legal officer, previously served as chief legal officer and corporate secretary of Rubius Therapeutics. Prior to joining Rubius, she served as General Counsel at Synlogic, uniQure, and Forum Pharmaceuticals.