MICA

Preliminary data from CLN-619 in combination with checkpoint inhibitor pembrolizumab show objective responses in patients with tumor types that are typically unresponsive to pembrolizumab, such as non-small cell lung cancer (NSCLC) with oncogenic mutations Longer term follow-up for patients treated with CLN-619 monotherapy demonstrates durable clinical benefit across multiple tumor types CLN-619 continues to demonstrate a favorable safety profile and is well tolerated both as monotherapy and in combination with pembrolizumab Based on observed clinical activity, Cullinan has initiated additional monotherapy and combination therapy expansion cohorts in NSCLC CAMBRIDGE, Mass., May 23, 2024 (GLOBE NEWSWIRE) -- Cullinan Therapeutics, Inc. (Nasdaq: CGEM), a biopharmaceutical company focused on developing modality-agnostic targeted therapies, today announced first clinical data from its Phase 1 dose escalation cohort of CLN-619 in combination with checkpoint inhibitor (CPI) pembrolizumab and updated results from the monotherapy dose escalation cohort in patients with advanced solid tumors. Findings from the clinical trial will be shared at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting as a poster presentation during the “Developmental Therapeutics—Immunotherapy” session (Abstract #2588, Poster Bd 67) on June 1, 2024, 9:00 AM-12:00 PM Central Time. Summary of Key Clinical Results from Combination Arm of Phase 1 Clinical Trial in Patients with Solid Tumors Of 22 patients treated with CLN-619 in combination with pembrolizumab, 18 were RECIST-evaluable for response.Confirmed partial responses (PR) were observed in 3 patients treated with CLN-619 at doses ≥3mg/kg in combination with pembrolizumab.Responses were observed in patients with tumor types not typically responsive to CPI treatment. Characteristics of Responders Tumor TypeNumber ofPrior Linesof TherapyPrior CPICPI ResponsiveTumor (Yes/No?)BestResponseDuration ofResponse (Weeks)NSCLC, EGFR exon 18/216NoNoPR24NSCLC, ALKr2NoNoPR12.7Gastric, HER2+3NoYesPR8.9+ (ongoing) Summary of Efficacy in NSCLC (Monotherapy and Combination Cohorts) Objective responses and stable disease (SD) were observed in patients with NSCLC with oncogenic mutations in the CLN-619 monotherapy and combination cohorts. 8 of the 11 patients with NSCLC were RECIST-evaluable; of these, 6 had oncogenic mutations.3 of the 6 patients with oncogenic mutations experienced clinical benefit – there were 2 PRs and 1 SD lasting >18 weeks. Summary of Updated Key Clinical Results from Monotherapy Arm of Phase 1 Clinical Trial in Patients with Solid Tumors Among 42 patients treated with CLN-619 monotherapy, 29 received CLN-619 at a dose ≥1 mg/kg and were RECIST-evaluable.The clinical benefit rate (CBR) was 41.4% (1 complete response (CR), 2 PR, 9 SD ≥18 weeks). Characteristics of Patients with Response or SD ≥18 Weeks Tumor TypeNumber ofPrior Lines ofTherapyBestResponseDuration ofResponse(Weeks)Responders (n=3) Mucoepidermoid parotid2CR71Endometrial (serous, MMRp)5PR31Endometrial (endometrioid, MMRp)3PR55+ (ongoing)SD ≥18 weeks (n=9) Cervical squamous (n=2); breast (ER/PR+, HER2−; n=1); ovarian (n=1); endometrial carcinosarcoma (n=1); mediastinal intimal sarcoma (n=1); adenoid cystic carcinoma (n=1); pancreatic adenocarcinoma (KRAS G12V; n=1); NSCLC (STK11m; n=1)Mean: 3.6Range: 1–7SD ≥18 wksRange: 18–56 Summary of Safety Data CLN-619 was well tolerated in combination with pembrolizumab and as monotherapy. Most treatment-related adverse events (TRAEs) were grade 1/2. TRAEs reported in ≥10% of safety-evaluable patients (combination: n=22; monotherapy: n=42) were infusion-related reactions (IRRs) (combination: 18.2%; monotherapy: 28.6%) and fatigue (combination: 18.2%; monotherapy: 9.5%). The only grade ≥3 TRAE reported in >5% of patients in any group was increased AST (combination: 0; monotherapy: 7.1%). One patient in each cohort discontinued study treatment due to TRAEs (4.5% combination and 2.4% monotherapy). There were no treatment-related deaths. IRR was the most frequently reported TRAE with CLN-619. With administration of prophylactic pre-medications, most IRRs were grade 1 or 2, occurred on Day 1 of Cycle 1, and resolved quickly. “Our initial clinical findings show that the combination of CLN-619, a novel antibody targeting MICA/B, with pembrolizumab may benefit patients whose cancer is not typically amenable to checkpoint inhibitor therapy. More specifically, we observed objective responses in patients with ALK- and EGFR-mutated NSCLC who had relapsed after tyrosine kinase inhibitors (TKIs), patients who do not typically respond to checkpoint inhibitors,” said Jeffrey Jones, MD, MBA, Chief Medical Officer, Cullinan Therapeutics. “Additionally, longer-term follow-up for patients treated with CLN-619 monotherapy shows favorable safety and durable clinical benefit with extended treatment, including objective responses and prolonged stable disease in multiple tumor types and in patients with disease progression after CPI therapy. We are encouraged by these data and have initiated monotherapy and combination expansion cohorts in NSCLC.” “There remains significant unmet need for patients with NSCLC with oncogenic mutations relapsing after TKIs, so we see a potential benefit in novel therapies that can be easily combined with established CPIs,” said Alexander Spira, MD, PhD, FACP, FASCO, Director, Virginia Cancer Specialists Research Institute and Director, NEXT Oncology Virginia. “Combining CLN-619 with pembrolizumab engages multiple immune effector cells, including innate cells by CLN-619 and T cells by pembrolizumab. The safety profile of CLN-619 along with the biologic rationale for combination with CPI make this a potentially synergistic approach.” CLN-619 Further Development Plan CLN-619 is being studied in an ongoing Phase 1 clinical trial (NCT05117476) both as monotherapy and in combination with pembrolizumab. The study design allows dose level extensions as well as expansion in tumor-specific cohorts. Consistent with prespecified criteria and based on initial safety and efficacy observations, Cullinan has initiated monotherapy and combination expansion cohorts in NSCLC. Enrollment continues in previously declared expansion cohorts in cervical (monotherapy) and endometrial cancers (monotherapy and combination). CLN-619 will also be studied in a Phase 1 clinical trial (NCT06381141) in patients with relapsed/refractory multiple myeloma. Virtual and Live Investor Event Cullinan Therapeutics will host an Investor Event on Saturday, June 1, 2024, at 6:30 PM Central Time, during which Dr. Jeff Jones, Chief Medical Officer at Cullinan Therapeutics, will present the CLN-619 data shared at the 2024 ASCO Annual Meeting, and Dr. Alexander Spira, Director, Virginia Cancer Specialists Research Institute and Director, NEXT Oncology Virginia, will share an overview of the current treatment landscape for EGFR-mutated NSCLC. Investors and analysts are invited to register to attend in person by emailing Chad Messer, VP Investor Relations (cmesser@cullinantx.com). A live webcast will be available via the events page of the Company’s investor relations website at https://cullinantherapeutics.com/events-and-presentations/ and a replay will be available shortly after the conclusion of the live event. About CLN-619 CLN-619 is a potential first-in-class humanized IgG1 monoclonal antibody that binds to the stress induced ligands MICA and MICB, which are expressed on a wide variety of solid tumors and hematologic malignancies. Engagement of MICA/B by the activating receptor NKG2D, present on both cytotoxic innate and adaptive immune cells, results in target cell lysis. However, tumor cells can shed MICA/B via proteases they release into the tumor microenvironment, resulting in evasion of immune-mediated destruction. CLN-619 functions by restoring MICA/B expression on the surface of tumor cells to reinvigorate NKG2D-mediated immune activation, and by inducing antibody-dependent cellular toxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), together promoting anti-tumor activity via multiple immune-mediated mechanisms. CLN-619 is being studied in an ongoing Phase 1 clinical trial (NCT05117476) both as a monotherapy and in combination with pembrolizumab. The study design allows dose level extensions as well as expansion in tumor-specific cohorts. CLN-619 will also be studied in a Phase 1 clinical trial (NCT06381141) in patients with relapsed/refractory multiple myeloma. About Cullinan Therapeutics Cullinan Therapeutics, Inc. (Nasdaq: CGEM) is a biopharmaceutical company dedicated to creating new standards of care for patients. We have strategically built a diversified portfolio of clinical-stage assets that inhibit key drivers of disease or harness the immune system to eliminate diseased cells in both oncology and autoimmune diseases. Our portfolio encompasses a wide range of modalities, each with the potential to be best and/or first in class. Anchored in a deep understanding of oncology, immunology, and translational medicine, we create differentiated ideas, identify the most appropriate targets, and select the optimal modality to develop transformative therapeutics across a wide variety of cancer and autoimmune indications. We push conventional boundaries from candidate selection to differentiated therapeutic, applying rigorous go/no go criteria at each stage of development to fast-track only the most promising molecules to the clinic and, ultimately, commercialization. With deep scientific expertise, our teams exercise creativity and urgency to deliver on our promise to bring new therapeutic solutions to patients. Learn more about our Company at https://cullinantherapeutics.com/, and follow us on LinkedIn and X. Forward-Looking Statements This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. These forward-looking statements include, but are not limited to, express or implied statements regarding Cullinan’s beliefs and expectations regarding the potential benefits and therapeutic potential of CLN-619; our clinical development plans and timelines; our plans regarding future data presentations and other statements that are not historical facts. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “hope,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “target,” “should,” “would,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management's current expectations and beliefs of future events and are subject to known and unknown risks and uncertainties that may cause our actual results, performance or achievements to be materially different from any expressed or implied by the forward-looking statements. These risks include, but are not limited to, the following: uncertainty regarding the timing and results of regulatory submissions; success of our clinical trials and preclinical studies; risks related to our ability to protect and maintain our intellectual property position; risks related to manufacturing, supply, and distribution of our product candidates; the risk that any one or more of our product candidates, including those that are co-developed, will not be successfully developed and commercialized; the risk that the results of preclinical studies or clinical studies will not be predictive of future results in connection with future studies; and success of any collaboration, partnership, license or similar agreements. These and other important risks and uncertainties discussed in our filings with the Securities and Exchange Commission, including under the caption “Risk Factors” in our most recent Annual Report on Form 10-K and subsequent filings with the SEC, could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change, except to the extent required by law. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release. Moreover, except as required by law, neither the company nor any other person assumes responsibility for the accuracy and completeness of the forward-looking statements included in this press release. Any forward-looking statement included in this press release speaks only as of the date on which it was made. Contacts: Investor RelationsChad Messer+1 203.464.8900cmesser@cullinantx.com MediaRose Weldon+1 215.801.7644rweldon@cullinantx.com Download MICA/B Fact Sheet: http://ml.globenewswire.com/Resource/Download/7168ad37-1dd9-4188-9221-c889232f8e8b Watch MICA/B Video: https://www.globenewswire.com/NewsRoom/AttachmentNg/55b7b23f-17e3-42d1-81b9-6ef59a9d92ec

CAMBRIDGE, Mass., April 24, 2024 (GLOBE NEWSWIRE) -- Cullinan Therapeutics, Inc. (Nasdaq: CGEM), a biopharmaceutical company focused on modality-agnostic targeted therapies, today announced that clinical data from its Phase 1 trial of CLN-619 in patients with advanced solid tumors will be presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting taking place in Chicago from May 31-June 4, 2024. The data will include first results from the dose escalation cohort of CLN-619 in combination with checkpoint inhibitor pembrolizumab and updated results from the monotherapy dose escalation cohort in patients with advanced solid tumors. “We are pleased to present our initial clinical findings for CLN-619 plus pembrolizumab in patients with solid tumors at ASCO 2024, along with updated results from our monotherapy dose escalation study. CLN-619 is a novel, potential first-in-class antibody that binds to MICA and MICB stress-induced ligands that engage the activating receptor NKG2D, present on both innate and adaptive immune cells. CLN-619 exerts its effects through multiple mechanisms, providing an opportunity to combine CLN-619 with immunotherapies that target potentially synergistic immune activation pathways, such as checkpoint inhibitors,” said Jeffrey Jones, MD, MPH, MBA, Chief Medical Officer, Cullinan Therapeutics. The details of the presentation include: Poster Title: CLN-619 (anti-MICA/B antibody) alone and in combination with pembrolizumab for advanced solid tumors: Updated results of a Ph1 study Author: Dr. Ignacio Melero, et al. Poster Number: 2588 Session: Developmental Therapeutics—Immunotherapy Session Date and Time: June 1, 2024, 9:00 AM-12:00 PM Central Time About CLN-619 CLN-619 is a potential first-in-class humanized IgG1 monoclonal antibody that binds to the stress induced ligands MICA and MICB, which are expressed on a wide variety of solid tumors and hematologic malignancies. Engagement of MICA/B by the activating receptor NKG2D, present on both cytotoxic innate and adaptive immune cells, results in target cell lysis. However, tumor cells can shed MICA/B via proteases they release into the tumor microenvironment, resulting in evasion of immune-mediated destruction. CLN-619 functions by restoring MICA/B expression on the surface of tumor cells to reinvigorate NKG2D-mediated immune activation, and by inducing antibody-dependent cellular toxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), together promoting anti-tumor activity via multiple immune-mediated mechanisms. CLN-619 is being studied in an ongoing Phase 1 clinical trial (NCT05117476) both as a monotherapy and in combination with pembrolizumab. The study design allows dose level extensions as well as expansion in tumor-specific cohorts. CLN-619 will also be studied in a Phase 1 clinical trial (NCT06381141) in patients with relapsed/refractory multiple myeloma. About Cullinan Therapeutics Cullinan Therapeutics, Inc. (Nasdaq: CGEM) is a biopharmaceutical company dedicated to creating new standards of care for patients. We have strategically built a diversified portfolio of clinical-stage assets that inhibit key drivers of disease or harness the immune system to eliminate diseased cells in both oncology and autoimmune diseases. Our portfolio encompasses a wide range of modalities, each with the potential to be best and/or first in class. Anchored in a deep understanding of oncology, immunology, and translational medicine, we create differentiated ideas, identify the most appropriate targets, and select the optimal modality to develop transformative therapeutics across a wide variety of cancer and autoimmune indications. We push conventional boundaries from candidate selection to differentiated therapeutic, applying rigorous go/no go criteria at each stage of development to fast-track only the most promising molecules to the clinic and, ultimately, commercialization. With deep scientific expertise, our teams exercise creativity and urgency to deliver on our promise to bring new therapeutic solutions to patients. Learn more about our Company at , and follow us on LinkedIn and X. Forward-Looking Statements This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. These forward-looking statements include, but are not limited to, express or implied statements regarding Cullinan’s beliefs and expectations regarding the potential benefits and therapeutic potential of CLN-619; our clinical development plans and timelines; our plans regarding future data presentations and other statements that are not historical facts. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “hope,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “target,” “should,” “would,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management's current expectations and beliefs of future events and are subject to known and unknown risks and uncertainties that may cause our actual results, performance or achievements to be materially different from any expressed or implied by the forward-looking statements. These risks include, but are not limited to, the following: uncertainty regarding the timing and results of regulatory submissions; success of our clinical trials and preclinical studies; risks related to our ability to protect and maintain our intellectual property position; risks related to manufacturing, supply, and distribution of our product candidates; risks related to the impact of COVID-19 affecting countries or regions in which we have operations or do business, including potential negative impacts on our employees, customers, supply chain and production as well as global economies and financial markets; the risk that any one or more of our product candidates, including those that are co-developed, will not be successfully developed and commercialized; the risk that the results of preclinical studies or clinical studies will not be predictive of future results in connection with future studies; and success of any collaboration, partnership, license or similar agreements. These and other important risks and uncertainties discussed in our filings with the Securities and Exchange Commission, including under the caption “Risk Factors” in our most recent Annual Report on Form 10-K and subsequent filings with the SEC, could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change, except to the extent required by law. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release. Moreover, except as required by law, neither Cullinan nor any other person assumes responsibility for the accuracy and completeness of the forward-looking statements included in this press release. Any forward-looking statement included in this press release speaks only as of the date on which it was made. Contacts: Investor Relations Chad Messer +1 203.464.8900 cmesser@cullinantx.com Media Rose Weldon +1 215.801.7644 rweldon@cullinantx.com

Company will initiate Phase 1 study of CLN-619 for relapsed or refractory multiple myeloma, first MICA/B antibody clinical study in hematologic malignancies Follows ongoing clinical study of CLN-619 alone and in combination with pembrolizumab in solid tumors, with anticipated updated clinical data in Q2 2024 March 01, 2024 -- Cullinan Oncology, Inc. (Nasdaq: CGEM), a biopharmaceutical company focused on modality-agnostic targeted oncology therapies, today announced the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for CLN-619 in relapsed/refractory multiple myeloma. CLN-619 is a potential first-in-class humanized IgG1 monoclonal antibody that binds to stress-induced ligands, MICA and MICB, which are expressed on a wide variety of solid tumors and hematologic malignancies. The company will commence a Phase 1 dose-escalation and dose-expansion trial of CLN-619. “Multiple myeloma remains incurable, and most patients experience sequential relapses. The response to treatment is typically shorter with each relapse, so novel treatments are still needed,” said Jeffrey Jones, MD, MPH, MBA, Chief Medical Officer, Cullinan Oncology. “Multiple myeloma is another example of a malignancy where MICA/B shedding from tumor cells allows for immune evasion. As we shared at SITC 2023, CLN-619 restores MICA/B expression on tumor cells, enabling immune recognition. This Phase 1 trial will assess CLN-619 in patients with multiple myeloma, and, given the safety profile shown to date for CLN-619, we believe there is an opportunity to combine the monoclonal antibody with multiple standard therapies. With clinical studies in both solid tumors and hematologic malignancies, we look forward to assessing the full potential of CLN-619 to address multiple areas of unmet clinical need.” CLN-619 is a potential first-in-class humanized IgG1 monoclonal antibody that binds to the stress-induced ligands MICA and MICB, which are expressed on a wide variety of solid tumors and hematologic malignancies. Engagement of MICA/B by the activating receptor NKG2D, present on both cytotoxic innate and adaptive immune cells, results in target cell lysis. However, tumor cells can shed MICA/B via proteases they release into the tumor microenvironment, resulting in evasion of immune-mediated destruction. CLN-619 functions by restoring MICA/B expression on the surface of tumor cells, enhancing the interaction between MICA and NKG2D, and inducing antibody-dependent cellular toxicity (ADCC), together promoting anti-tumor activity via multiple immune-mediated mechanisms. CLN-619 is being studied in an ongoing Phase 1 clinical trial (NCT05117476) both as a monotherapy and in combination with pembrolizumab in patients with solid tumors. The study design allows dose level extensions as well as expansion in tumor-specific cohorts. CLN-619 will also be studied in a Phase 1 clinical trial in patients with relapsed/refractory multiple myeloma. Cullinan Oncology, Inc. (Nasdaq: CGEM) is a biopharmaceutical company dedicated to creating new standards of care for patients with cancer. We innovate without borders to find the most promising clinic-ready cancer therapies, whether from our own discovery efforts or through exceptional engagement with our academic and industry partners. Anchored in a deep understanding of immuno-oncology and translational cancer medicine, we leverage our scientific excellence in small molecules and biologics to create differentiated ideas, identify unique targets, and select the optimal modality to develop transformative therapeutics across cancer indications. Powered by our novel research model, we push conventional boundaries from candidate selection to cancer therapeutic, applying rigorous early experimentation to fast-track only the most promising assets to the clinic and ultimately commercialization. As a result, our diversified pipeline is strategically built with assets that activate the immune system or inhibit key oncogenic drivers across a wide range of modalities, each with the potential to be the best or first in their class. Our people possess deep scientific expertise, seek innovation openly, and exercise creativity and urgency to deliver on our promise to bring new therapeutic solutions to patients with cancer. Learn more about our Company at www.cullinanoncology.com, and follow us on LinkedIn and Twitter. The content above comes from the network. if any infringement, please contact us to modify.