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Adaptimmune and TCR² Therapeutics Announce Strategic Combination to Create a Preeminent Cell Therapy Company for Solid Tumors
March 06 2023 - 06:00AM
GlobeNewswire Inc.
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Adaptimmune Therapeutics plc (Nasdaq: ADAP) and TCR² Therapeutics Inc. (Nasdaq: TCRR), today announced entry into a definitive agreement under which Adaptimmune will combine with TCR² in an all-stock transaction to create a preeminent cell therapy company focused on treating solid tumors. The combination provides extensive benefits for clinical development and product delivery supported by complementary technology platforms. As a result, and following the closing of the transaction, it is anticipated that the combined company’s cash runway will extend into 2026.
The lead clinical franchises for the combined company utilize engineered T-cell therapies targeting MAGE-A4 and mesothelin. These targets are expressed on a broad range of solid tumors and are supported by compelling early- and late-stage clinical data. The combined company also has a preclinical pipeline of additional target opportunities with development initially focused on PRAME and CD70.
Adrian Rawcliffe, Adaptimmune’s Chief Executive Officer: “This strategic combination takes two technologically and culturally aligned companies at the forefront of their fields and combines them to create a preeminent cell therapy company for solid tumors. The combined company will drive forward its pipeline of cell therapies aimed at treating multiple cancers with high unmet medical needs. This includes gaining approval for the first engineered TCR T-cell therapy for a solid tumor – afami-cel for the treatment of synovial sarcoma. With our cash runway anticipated to be extended into 2026 and covering multiple clinical catalysts in cancers with significant market potential, the combined company is well placed to develop cell therapies as a mainstream option for people with cancer.”
Garry Menzel, Ph.D., President and Chief Executive Officer of TCR2 Therapeutics: “The strategic rationale for this combination and the operating benefits are highly compelling for both Adaptimmune and TCR² shareholders. The combination of our two companies not only sets the stage for near-term execution but also positions the new company for the longer-term. We jointly have an array of next-generation innovations that we will integrate to address the tumor micro-environment using both autologous and allogeneic approaches. Focus and specialization are critical in the cell therapy space and we believe the combined company has the technologies necessary to succeed. I am delighted that this combination provides a strong foundation to commercialize curative therapies for people with cancer.”
Significant Solid Tumor Opportunity
Solid tumors represent approximately 90% of all cancers. The combined company’s clinical programs targeting MAGE-A4 or mesothelin can address multiple solid tumor indications with the potential to treat >300,000 patients per year in the EU and US.
For patients with tumors potentially expressing MAGE-A4 and mesothelin, the combined company plans to screen for both targets to identify eligible patients.
In addition, the preclinical pipeline, including PRAME and CD70, could expand the addressable population.
Complementary Technology Platforms
The combined company will possess two clinically validated and complementary platforms in SPEAR and TRuC T-cells enabling engagement of both intracellular targets (with SPEAR) and extracellular targets (with TRuC), thus broadening the potential number of addressable cancers.
Adaptimmune’s proprietary SPEAR T-cell technology is based on the affinity enhancement and engineering of T-cell receptors (TCRs) to target solid tumor-specific peptide: HLA complexes.
TCR2’s proprietary TRuC T-cell technology uses an antibody-based binding domain fused to TCR subunits to reprogram an intact TCR complex to recognize tumor surface antigens.
Both technologies can be further leveraged in the combined company’s allogeneic platform.
Highly Specialized Talent and Operational Benefits
The novelty, complexity, and rapid growth of the cell therapy field has highlighted the need for companies to develop specialized capabilities with a goal of delivering treatments that are both curative and mainstream.
To this end, over the last decade, the teams at Adaptimmune and TCR2 have been responsible for successfully advancing multiple programs from preclinical concept to late-stage products.
The combined company, located in key innovation hubs, will have a deep bench of cell therapy professionals, infrastructure, and end-to-end capabilities.
Value-Creating Catalysts (see Exhibit A for combined clinical pipeline)
Following closing of the transaction, the combined company is anticipated to have a cash runway into 2026 providing operational benefits and enables delivery of key catalysts, including:
2023
Products targeting MAGE-A4
Afami-cel
Completion of BLA submission for the treatment of synovial sarcoma. Anticipated mid-year.
Supported by compelling clinical data from the pivotal SPEARHEAD-1 trial with a response rate of 39% after a single dose and a duration of 12 months.
ADP-A2M4CD8 (next-generation product)
Expected full data readout from the monotherapy portion of the Phase 1 SURPASS trial in heavily pre-treated patients across a broad range of solid tumors.
Initiation of the Phase 2 SURPASS-3 trial in combination with nivolumab for platinum resistant ovarian cancer. This trial has the potential to become registrational.
Initiation of additional cohorts in the Phase 1 SURPASS trial in combination with pembrolizumab to treat patients in the first-line treatment setting for head & neck cancer and second-line setting for urothelial cancer.
ADP-A2M4CD8 has demonstrated a 52% response rate in the focus indications of ovarian, urothelial, and head & neck cancers, which improves to a 75% response rate in patients who received 3 or few prior lines of therapy.
Products targeting mesothelin
Gavo-cel
First readout from the Phase 2 portion of the gavo-cel clinical trial in platinum resistant or refractory ovarian cancer. Anticipated year-end.
Interim update, including key translational data, in patients with mesothelioma treated with gavo-cel in the Phase 2 clinical trial before the focus was narrowed to ovarian cancer. Anticipated mid-year.
Tumor regression has been observed in 93% of patients in the Phase 1 trial. The response rate was 29% in patients with ovarian cancer with a progression free survival of 5.8 months and overall survival of 8.1 months. The response rate in mesothelioma was 21% with a progression free survival of 5.9 months and overall survival of 11.2 months.
TC-510 (next-generation product)
First data readout from the Phase 1 trial with TC-510 for patients with ovarian, malignant pleural mesothelioma (MPM), pancreatic, colorectal, or triple negative breast cancer (TNBC). Anticipated year-end.
Preclinical
PRAME program to be IND ready.
2024
Products targeting MAGE-A4
Afami-cel
Potential PDUFA/FDA approval; would be the first marketed engineered TCR T-cell therapy for a solid tumor indication, if approved (synovial sarcoma)
ADP-A2M4CD8 (next-generation product)
First readout from SURPASS-3 trial in ovarian cancer
First readout for head and neck cancer cohort in the Phase 1 SURPASS trial
First readout for urothelial cancer cohort in the Phase 1 SURPASS trial
Products targeting mesothelin
Gavo-cel and TC-510
Readout from gavo-cel Phase 2 trial in platinum resistant ovarian cancer
Readout from TC-510 Phase 1 trial and selection of dose to carry forward into additional late-phase trials
Preclinical
CD70 program (TC-520) to be IND ready
Transaction details for strategic combination
The merger agreement was unanimously approved by the boards of directors of both companies. TCR2 stockholders will receive 1.5117 Adaptimmune ADS for each TCR2 share.
Following the closing of the transaction, Adaptimmune shareholders will own approximately 75% of the combined company and TCR2 stockholders will own approximately 25% of the combined company.
Subject to shareholder approval and the subsequent closing of the transaction, the combined company is expected to continue to trade on the Nasdaq Stock Market under the symbol “ADAP”. The combined company has a team of leading cell therapy experts led by Adrian Rawcliffe, the CEO of Adaptimmune. The Board of Directors, composed of three members from TCR2 and six continuing from Adaptimmune, is expected to be: David Mott (Chair); Andrew Allen, M.D., Ph.D.; Lawrence Alleva; Ali Behbahani, M.D.; John Furey; Priti Hegde, Ph.D.; Garry Menzel, Ph.D.; Adrian Rawcliffe, and Elliott Sigal, M.D., Ph.D. (who will step down on November 1, 2023 when Kristen Hege, M.D. joins the Board of Directors).
The transaction is currently expected to close in Q2 2023, subject to the receipt of approvals by Adaptimmune shareholders and TCR2 stockholders and satisfaction or waiver of other closing conditions.
Adaptimmune Full Year 2022 Financial Results
In a separate press release, Adaptimmune will announce its Q4 and full year 2022 financial results and business updates, which will be available on the “Investor Relations” section of the Adaptimmune website.
Advisors
TD Cowen is serving as financial advisor to Adaptimmune and Ropes & Gray LLP is serving as legal counsel to Adaptimmune. Piper Sandler is serving as financial advisor to TCR2 and Goodwin Procter LLP is serving as legal counsel to TCR2.
Forward-Looking Statements
This communication relates to the proposed transaction pursuant to the terms of the Agreement and Plan of Merger, dated March 05, 2023, by and among Adaptimmune Therapeutics plc (“Parent”), CM Merger Sub, Inc. (“Merger Sub”), and TCR² Therapeutics Inc. (the “Company”). This communication includes express or implied forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), about the proposed transaction between the Company and Parent and the operations of the combined company that involve risks and uncertainties relating to future events and the future performance of Parent and the Company. Actual events or results may differ materially from these forward-lo
jondoeuk
3 years ago
While the ORR dropped, PFS and OS data look pretty solid considering late line patients, and suggest responses are durable especially compared to benchmark data.
Once the PhII expansion is initiated they will assess gavo-cel efficacy in four indications (malignant pleural mesothelioma, NSCLC, ovarian and cholangiocarcinoma), evaluate combinations with an anti-PD-1, allow for retreatment on progression or if stable disease, and test alternate mesothelin expression cutoff levels.
In addition, an IND will be filed this year for a second gen version of gavo-cel (which has a cell intrinsic PD-1-CD28 'switch') [1], they are working on other enhancements, including IL-15, dual TRuCs, and even an allo platform [2].
Refs:
1 https://cancerres.aacrjournals.org/content/80/16_Supplement/893
2 https://cancerres.aacrjournals.org/content/80/16_Supplement/2190
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