On November 7, 2024 IMUNON, Inc. (NASDAQ: IMNN), a clinical-stage company in late-stage development with its DNA-mediated immunotherapy, reported the presentation of new clinical data from the recently completed Phase 2 OVATION 2 Study of IMNN-001, its investigational interleukin-12 (IL-12) immunotherapy for the treatment of advanced ovarian cancer based on the company’s proprietary TheraPlas technology (Press release, IMUNON, NOV 7, 2024, View Source [SID1234648577]). Results will be highlighted in a late-breaking poster session at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 39th Annual Meeting, taking place November 6-10, 2024, in Houston, Texas and virtually.

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IMNN-001 is an IL-12 DNA plasmid vector encased in a nanoparticle delivery system that enables cell transfection followed by persistent, local production and secretion of the IL-12 protein. IL-12 is one of the most active pluripotent cytokines for the induction of strong anti-cancer immunity acting through the induction of T-lymphocyte and natural killer cell proliferation, inhibiting tumor mediated immune suppression.

A total of 112 patients with newly diagnosed advanced ovarian cancer (intent-to-treat population) were enrolled in the Phase 2 OVATION 2 Study with a median follow-up of 24 months. Study participants were randomized 1:1 to evaluate the safety and efficacy of IMNN-001 (100 mg/m2 administered intraperitoneally weekly) plus neoadjuvant and adjuvant chemotherapy (NACT) of paclitaxel and carboplatin compared to standard-of-care NACT alone. The results being presented at the SITC (Free SITC Whitepaper) Annual Meeting, as of June 21, 2024, demonstrated:

Patients treated with IMNN-001 plus standard-of-care NACT lived 11.1 months (35%) longer than patients treated with NACT alone with a median overall survival (OS) of 40.5 months and 29.4 months, respectively (hazard ratio 0.74).
IMNN-001 treatment was associated with better surgical outcomes compared to NACT alone with a surgical response rate of 64.6% and 52.1%, respectively. The chemotherapy response score, another measure of treatment benefit, was 26.1% in the IMNN-001 treatment group versus 13.0% in the control group.
IMNN-001 was also associated with an improvement in progression-free survival (PFS) with a median PFS of 14.9 months in the IMNN-001 treatment group compared to 11.9 months in the control group (hazard ratio 0.79).
The rate of complete response for best overall response, a measure of tumor shrinkage, was comparable across all study participants (n=1 in both groups, or 1.7% in IMNN-001 treatment group, 1.9% in the control group) when measured early in the study at debulking surgery.
In a subgroup analysis of patients who received a PARP inhibitor as maintenance therapy, patients in the IMNN-001 treatment arm had a median PFS of 33.8 months versus 22.1 months in the control arm (hazard ratio 0.80) and median OS was not reached for the treatment arm versus 37.1 months for the control arm.
IMNN-001 was generally well tolerated, with the most common adverse events (AEs) primarily gastrointestinal events (abdominal pain, nausea, vomiting). Pain management protocols were found to be effective. There were no reports of cytokine release syndrome or any other serious immune related AEs.
"These results from OVATION 2, including overall survival and progression-free survival among women with advanced ovarian cancer treated with IMNN-001 and NACT compared to standard-of-care NACT alone, reflect a meaningful improvement and show consistency across various endpoints and patient subgroups," said Stacy Lindborg, Ph.D., president and chief executive officer of IMUNON. "This consistency brings great hope and excitement that these results can be replicated in Phase 3, and that IMNN-001 may offer a significant advancement in the treatment landscape for ovarian cancer. We look forward to our end-of-Phase 2 in-person meeting with the FDA to discuss plans for the Phase 3 pivotal trial, which we expect to start in the first quarter of next year."

"IMNN-001 is the first immunotherapy to achieve a clinically effective response in ovarian cancer, including benefits in both progression-free and overall survival, let alone in a first-line treatment setting," said study investigator and presenter Jennifer Scalici, M.D., Professor, Division of Gynecological Oncology, Emory University School of Medicine. "It is also especially encouraging that IMNN-001 offers benefits when used alongside PARP inhibitors, which have been very important in the treatment of advanced ovarian cancer but still present limitations in terms of OS benefits. There is a significant unmet need in treating women with ovarian cancer, which is the second deadliest gynecologic malignancy, and the promising results from the OVATION 2 Study represent the potential of IMNN-001 to offer a much-needed treatment option."

The details of the SITC (Free SITC Whitepaper) poster presentation are as follows:

Abstract Title: Phase I/II study of Safety and Efficacy of Intraperitoneal IMNN-001 with Neoadjuvant Chemotherapy of Paclitaxel and Carboplatin in Patients Newly Diagnosed with Advanced Epithelial Ovarian Cancer
Presenting Author: Jennifer Scalici, M.D., Professor, Division of Gynecological Oncology, Emory University School of Medicine
Date: Friday, November 8, 2024
Time: 12:15-1:45 p.m. and 5:30 – 7:00 p.m. CST
Abstract Number: 1505

As previously announced, IMUNON plans to hold an End-of-Phase 2 meeting with the U.S. Food and Drug Administration (FDA) in person to discuss the design for a Phase 3 pivotal study of IMNN-001 in advanced ovarian cancer, with the trial expected to start in the first quarter of 2025.

About the Phase 2 OVATION 2 Study

OVATION 2 evaluated the dosing, safety, efficacy and biological activity of intraperitoneal administration of IMNN-001 in combination with neoadjuvant and adjuvant chemotherapy (NACT) of paclitaxel and carboplatin in patients newly diagnosed with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer. Treatment in the neoadjuvant period is designed to shrink the tumors as much as possible for optimal surgical removal after three cycles of chemotherapy. Following NACT, patients undergo interval debulking surgery, followed by three additional cycles of adjuvant chemotherapy to treat any residual tumor. This open-label study enrolled 112 patients who were randomized 1:1 and evaluated for safety and efficacy to compare NACT plus IMNN-001 versus standard-of-care NACT. In accordance with the study protocol, patients randomized to the IMNN-001 treatment arm could receive up to 17 weekly doses of 100 mg/m2 in addition to NACT. As a Phase 2 study, OVATION 2 was not powered for statistical significance. Additional endpoints included objective response rate, chemotherapy response score and surgical response.

About IMNN-001 Immunotherapy

Designed using IMUNON’s proprietary TheraPlas platform technology, IMNN-001 is an IL-12 DNA plasmid vector encased in a nanoparticle delivery system that enables cell transfection followed by persistent, local secretion of the IL-12 protein. IL-12 is one of the most active cytokines for the induction of potent anticancer immunity acting through the induction of T-lymphocyte and natural killer cell proliferation. IMUNON previously reported positive safety and encouraging Phase 1 results with IMNN-001 administered as monotherapy or as combination therapy in patients with advanced peritoneally metastasized primary or recurrent ovarian cancer, and completed a Phase 1b dose-escalation trial (the OVATION 1 Study) of IMNN-001 in combination with carboplatin and paclitaxel in patients with newly diagnosed ovarian cancer.

About Epithelial Ovarian Cancer

Epithelial ovarian cancer is the sixth deadliest malignancy among women in the U.S. There are approximately 20,000 new cases of ovarian cancer every year and approximately 70% are diagnosed in advanced Stage III/IV. Epithelial ovarian cancer is characterized by dissemination of tumors in the peritoneal cavity with a high risk of recurrence (75%, Stage III/IV) after surgery and chemotherapy. Since the five-year survival rates of patients with Stage III/IV disease at diagnosis are poor (41% and 20%, respectively), there remains a need for a therapy that not only reduces the recurrence rate, but also improves overall survival. The peritoneal cavity of advanced ovarian cancer patients contains the primary tumor environment and is an attractive target for a regional approach to immune modulation.

On November 7, 2024 ADC Therapeutics SA (NYSE: ADCT), a commercial-stage global leader and pioneer in the field of antibody drug conjugates (ADCs), reported financial results for the third quarter ended September 30, 2024, and provided recent operational updates (Press release, ADC Therapeutics, NOV 7, 2024, View Source [SID1234647915]).

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"We are excited about the advancements in our ZYNLONTA trials in earlier lines of diffuse large B-cell lymphoma therapy and look forward to reporting more on the combination with glofitamab in our LOTIS-7 trial, as well as reaching the expected full enrollment in LOTIS-5 before year-end," said Ameet Mallik, Chief Executive Officer of ADC Therapeutics. "We are discontinuing ADCT-601 targeting AXL and will prioritize our exatecan-based platform for solid tumors moving forward. With our expected cash runway into mid-2026, we believe we are well positioned to execute our strategy and advance multiple value-generating catalysts going forward."

Third Quarter 2024 Operational Updates & Recent Highlights

•Full enrollment expected by year-end in LOTIS-5.Enrollment for the Phase 3 confirmatory trial evaluating ZYNLONTA in combination with rituximab in patients with 2L+ diffuse large B-cell lymphoma (DLBCL) is expected to be completed by year-end 2024 with a data update expected in late 2025 once the pre-specified number of events is reached.

•LOTIS-7 enrollment continues with expected interim data update in December 2024.Enrollment continued in the Part 2 dose expansion of LOTIS-7, a Phase 1b open-label clinical trial evaluating ZYNLONTA in combination with the bispecific antibody glofitamab in patients with relapsed or refractory DLBCL. An interim update on safety and efficacy in a subset of patients is expected in December with additional data anticipated in the first half of 2025.

•Abstracts accepted for presentation at the 66th annual American Society of Hematology (ASH) (Free ASH Whitepaper) 2024 Annual Meeting. Updated data from the investigator-initiated Phase 2 clinical trial, conducted at the Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine, evaluating ZYNLONTA in combination with rituximab in patients with relapsed or refractory follicular lymphoma will be shared during an oral presentation titled, "Loncastuximab tesirine with rituximab induces robust and durable complete metabolic responses in high-risk relapsed/refractory follicular lymphoma" (Abstract #337) on December 7, 2024 at 4 p.m. PT.

Updated data from the investigator-initiated Phase 2 clinical trial, conducted at the Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine, evaluating ZYNLONTA for the treatment of relapsed or refractory marginal zone lymphoma (MZL) will be presented during a poster presentation titled, "Limited duration loncastuximab tesirine induces a high rate of complete responses in patients in relapsed/refractory marginal zone lymphoma – report of first planned interim futility analysis of a multicenter Phase II study" (Abstract #3032) on December 8, 2024 from 6 – 8 p.m. PT.

•Discontinuation of ADCT-601 program targeting AXL. Based on the available clinical data and capital requirements for continued development, the Company will discontinue the Phase 1b ADCT-601 program targeting AXL as a single agent and/or in combination for patients with sarcoma, pancreatic cancer and non-small cell lung cancer. Although early signs of antitumor activity were observed during the dose escalation phase, we were unable to demonstrate a favorable benefit-risk profile during the dose optimization/expansion phase.

•ADCT-602 targeting CD22 dose escalation progressing. The Phase 1/2 clinical trial, sponsored by The University of Texas MD Anderson Cancer Center, evaluating ADCT-602 in patients with relapsed or refractory B-cell acute lymphoblastic leukemia continues to progress and dose escalation continues at 60 µg/kg dose.

•IND-enabling studies ongoing in early-stage pipeline. Progress continues in the Investigational New Drug (IND) enabling studies for the Company’s exatecan-based programs for ADCs targeting Claudin-6, PSMA and NaPi2b, while our ASCT2 targeting ADC is in the drug candidate selection stage. The Company has selected one target to move toward IND which is expected to be disclosed in 2025.

Third Quarter and Year-to-Date 2024 Financial Results

•Product Revenues: ZYNLONTA generated net product revenues of $18.0 million for the third quarter ended September 30, 2024 and $52.9 million for the first nine months of 2024 as compared to $14.3 million and $52.4 million for the same periods in 2023. The quarter-over-quarter increase is driven by higher sales volume, a higher selling price and lower gross-to-net deductions. The year-to-date increase is primarily attributable to a higher price, partially offset by lower sales volume.

•Research and Development (R&D) Expense: R&D expense was $32.5 million and $82.5 million for the three and nine months ended September 30, 2024, respectively. This compares to R&D expense of $27.1 million and $96.8 million for the same periods in 2023. The increase during the three months ended September 30, 2024 is due primarily to focused investment in prioritized development programs, including ADCT-601 and ZYNLONTA. The decrease during the nine months ended September 30, 2024 is due primarily to the implementation of productivity initiatives and focused investment in prioritized development programs.

•Selling and Marketing (S&M) Expense: S&M expense was $10.7 million and $32.8 million for the three and nine months ended September 30, 2024, respectively. This compares to S&M expense of $13.7 million and $43.5 million for the same periods in 2023. The decreases in S&M expense were primarily due to lower marketing and advertising costs and personnel related expenses.

•General & Administrative (G&A) Expense: G&A expense was $10.0 million and $32.3 million for the three and nine months ended September 30, 2024, respectively. This compares to G&A expense of $9.6 million and $37.1 million for the same periods in 2023. The quarter-over-quarter increase in G&A expense was primarily related to higher personnel related expenses, partially offset by lower insurance costs while the year-to-date decrease was primarily related to lower personnel related expenses as well as lower insurance and IT expenses.

•Net Loss: Net loss for the quarter ended September 30, 2024 was $44.0 million, or a net loss of $0.42 per basic and diluted share, as compared to net loss of $46.7 million, or a net loss of $0.57 per basic and diluted share for the same period in 2023. Net loss for the nine months ended September 30, 2024 was $127.1 million, or a net loss of $1.35 per basic and diluted share, as compared to net loss of $155.0 million, or a net loss of $1.90 per basic and diluted share for the nine months ended September 30, 2023. The decrease for the three months ended September 30, 2024 is primarily related to higher revenues and a lower equity in net loss of our joint venture partially offset by higher operating expenses. The decrease for the nine months ended September 30, 2024 is primarily due to lower operating expenses.

•Adjusted Net Loss: Adjusted net loss, which is a non-GAAP financial measure, was $29.4 million, or an adjusted net loss of $0.28 per basic and diluted share for the quarter ended September 30, 2024 as compared to adjusted net loss of $32.4 million, or $0.39 per basic and diluted share, for the same period in 2023. Adjusted net loss for the nine months ended September 30, 2024 was $84.9 million, or an adjusted net loss of $0.90 per basic and diluted share, as compared to net loss of $106.3 million, or an adjusted net loss of $1.30 per basic and diluted share for the nine months ended September 30, 2023. The decrease in adjusted net loss for the three months ended September 30, 2024 is primarily related to higher revenues and a lower equity in net loss of our joint venture partially offset by higher operating expenses. The decrease in adjusted net loss for the nine months ended September 30, 2024 is primarily attributable to lower operating expenses.

•Cash and cash equivalents: As of September 30, 2024, cash and cash equivalents were $274.3 million, compared to $278.6 million as of December 31, 2023. In May 2024 the Company completed an underwritten offering resulting in net proceeds of approximately $97.4 million, extending the expected cash runway into mid-2026.

Conference Call Details

ADC Therapeutics management will host a conference call and live audio webcast to discuss third quarter 2024 financial results and provide a company update today at 8:30 a.m. Eastern Time. To access the conference call, please register here. The participant toll-free dial-in number is 1-800-836-8184 for North America and Canada. A live webcast of the call will be available under "Events & Presentations" in the Investors section of the ADC Therapeutics website at ir.adctherapeutics.com. The archived webcast will be available for 30 days following the call.

About ZYNLONTA

ZYNLONTA is a CD19-directed antibody drug conjugate (ADC). Once bound to a CD19-expressing cell, ZYNLONTA is internalized by the cell, where enzymes release a pyrrolobenzodiazepine (PBD) payload. The potent payload binds to DNA minor groove with little distortion, remaining less visible to DNA repair mechanisms. This ultimately results in cell cycle arrest and tumor cell death.

The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have approved ZYNLONTA (loncastuximab tesirine-lpyl) for the treatment of adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), DLBCL arising from low-grade lymphoma and also high-grade B-cell lymphoma. The trial included a broad spectrum of heavily pre-treated patients (median three prior lines of therapy) with difficult-to-treat disease, including

patients who did not respond to first-line therapy, patients refractory to all prior lines of therapy, patients with double/triple hit genetics and patients who had stem cell transplant and CAR-T therapy prior to their treatment with ZYNLONTA. This indication is approved by the FDA under accelerated approval and in the European Union under conditional approval based on overall response rate and continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Please see full prescribing information including important safety information about ZYNLONTA at www.ZYNLONTA.com.

ZYNLONTA is also being evaluated as a therapeutic option in combination studies in other B-cell malignancies and earlier lines of therapy.

On November 7, 2024 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, reported third quarter 2024 financial results and provided a corporate update (Press release, Kura Oncology, NOV 7, 2024, View Source [SID1234647932]).

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"We approach the end of 2024 in a strong position, with a series of important catalysts ahead," said Troy Wilson, Ph.D., J.D., President and Chief Executive Officer of Kura Oncology. "First, we look forward to sharing a robust dataset from more than 100 patients in our Phase 1a dose-escalation study of ziftomenib in combination with standards of care in acute myeloid leukemia (AML) at the upcoming American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, followed by topline results from our registration-directed trial of ziftomenib in relapsed/refractory (R/R) NPM1-mutant (NPM1-m) AML early next year. In the meantime, we continue to enroll rapidly across all our ziftomenib studies, further supporting the broad development of our menin inhibitor programs."

Recent Highlights

Topline results from registration-directed trial of ziftomenib in early 2025 – In May 2024, Kura completed enrollment of 85 patients in the Phase 2 portion of KOMET-001, a registration-directed clinical trial of its menin inhibitor, ziftomenib, in patients with R/R NPM1-m AML. Ziftomenib is the first and only investigational therapy to be granted Breakthrough Therapy Designation (BTD) for the treatment of R/R NPM1-m AML, which accounts for approximately 30% of new AML cases annually and represents a disease of significant unmet need for which no approved targeted therapy exists. Results from the Phase 1 portion of KOMET-001 were recently published in the leading clinical oncology journal, The Lancet Oncology.
Data from Phase 1a dose-escalation study of ziftomenib at ASH (Free ASH Whitepaper) – Two abstracts reporting preliminary data from the Phase 1a dose-escalation study of ziftomenib in combination with standards of care in patients with NPM1-m and KMT2A-rearranged (KMT2A-r) AML have been accepted for presentation at the ASH (Free ASH Whitepaper) Annual Meeting in December. As of the June 21, 2024 data cutoff, the abstracts continue to support a potential best-in-class safety and tolerability profile for ziftomenib, as well as robust and durable activity in combination with standards of care, including venetoclax plus azacitidine (ven/aza) as well as cytarabine plus daunorubicin (7+3). Kura expects to present a more mature dataset from more than 100 patients in the Phase 1a dose-escalation study in the presentations at ASH (Free ASH Whitepaper).
Phase 1b expansion study of ziftomenib now enrolling in all cohorts – All four cohorts in the Phase 1a dose-escalation study have cleared the highest dose and advanced into the Phase 1b expansion study at 600 mg. The Phase 1b expansion study includes multiple combination cohorts, including ziftomenib plus ven/aza in newly diagnosed NPM1-m or KMT2A-r AML and ziftomenib plus 7+3 in newly diagnosed NPM1-m or KMT2A-r AML without qualification for high-risk disease. Each of the seven combination cohorts is expected to enroll at least 20 patients. A total of 45 patients have already enrolled in the study since the first dose-expansion cohort opened in August 2024. The Company anticipates sharing preliminary data from the Phase 1b expansion study at a medical meeting in 2025.
Preclinical data support opportunity for ziftomenib in GIST – Last month, at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, Kura reported preclinical data supporting the combination of ziftomenib and imatinib for the treatment of advanced gastrointestinal stromal tumors (GIST). The combination showed unexpectedly robust and durable antitumor activity in both imatinib-sensitive and imatinib-resistant GIST patient-derived xenograft models, and in all cases was significantly superior to imatinib monotherapy. The Company received FDA clearance of its Investigational New Drug application for ziftomenib for the treatment of advanced GIST in August and expects to initiate a proof-of-concept study in the first half of 2025 evaluating ziftomenib and imatinib in patients with advanced GIST who have failed imatinib.
First patient dosed in study of KO-2806 and adagrasib in KRASG12C-mutated NSCLC – In August 2024, Kura began dosing patients in its study of KO-2806, a next-generation farnesyl transferase inhibitor (FTI), in combination with adagrasib in KRASG12C-mutated non-small cell lung cancer (NSCLC). The Company’s findings suggest that combining KO-2806 with adagrasib may drive tumor regressions and enhance both duration and depth of antitumor response in preclinical models of KRASG12C-mutated NSCLC. The study of KO-2806 and adagrasib is supported by a clinical collaboration and supply agreement with Mirati, now a Bristol Myers Squibb company.
Preclinical data support potential for menin inhibitor in diabetes – In June 2024, Kura reported data showing that ziftomenib induces insulin production, improves insulin sensitivity and reduces insulin resistance in a preclinical in vivo model of type 2 diabetes. Ziftomenib demonstrated meaningful levels of glycemic control, including reduced fasting blood glucose levels and %HbA1C within 27 days, as well as consistent improvement in both insulin sensitivity and insulin production. The data were presented at the American Diabetes Association Scientific Sessions in Orlando. The Company expects to nominate a next generation menin inhibitor candidate targeting diabetes in the first half of 2025.
Financial Results

Research and development expenses for the third quarter of 2024 were $41.7 million, compared to $29.3 million for the third quarter of 2023.
General and administrative expenses for the third quarter of 2024 were $18.2 million, compared to $13.1 million for the third quarter of 2023.
Net loss for the third quarter of 2024 was $54.4 million, compared to a net loss of $38.6 million for the third quarter of 2023. This included non-cash share-based compensation expense of $8.3 million, compared to $7.1 million for the same period in 2023.
As of September 30, 2024, Kura had cash, cash equivalents and short-term investments of $455.3 million, compared to $424.0 million as of December 31, 2023.
Based on its operating plan, management expects that cash, cash equivalents and short-term investments will fund current operations into 2027.
Forecasted Milestones

Present updated data from the KOMET-007 trial of ziftomenib in combination with ven/aza and 7+3 at ASH (Free ASH Whitepaper) in December 2024.
Report topline results from the KOMET-001 registration-directed trial of ziftomenib in NPM1-mutant R/R AML in early 2025.
Present preliminary data from the Phase 1b expansion portion of KOMET-007 at a medical meeting in 2025.
Initiate proof-of-concept study evaluating ziftomenib and imatinib in patients with advanced GIST in the first half of 2025.
Nominate a next generation menin inhibitor development candidate targeting diabetes in the first half of 2025.
Identify the maximum tolerated dose for KO-2806 as a monotherapy in the second half of 2024.
Initiate one or more expansion cohorts for the combination of KO-2806 and cabozantinib in renal cell carcinoma in the first half of 2025.
Present data from the KURRENT-HN trial of tipifarnib in combination with alpelisib in PIK3CA-dependent head and neck squamous cell carcinoma (HNSCC) in the first half of 2025.
Conference Call and Webcast

Kura’s management will host a webcast and conference call at 4:30 p.m. ET / 1:30 p.m. PT today, November 7, 2024, to discuss the financial results for the third quarter 2024 and to provide a corporate update. The live call may be accessed by dialing (800) 225-9448 for domestic callers and (203) 518-9708 for international callers and entering the conference ID: KURAQ3. A live webcast and archive of the call will be available online from the investor relations section of the company website at www.kuraoncology.com.

On November 7, 2024 Carisma Therapeutics Inc. (Nasdaq: CARM) ("Carisma" or the "Company"), a clinical-stage biopharmaceutical company focused on discovering and developing innovative immunotherapies, reported financial results for the quarter ended September 30, 2024, and highlighted recent business updates (Press release, Carisma Therapeutics, NOV 7, 2024, View Source [SID1234647948]).

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"Our recent progress across clinical and preclinical programs demonstrates our commitment to pioneering therapies that address significant unmet medical needs," said Steven Kelly, President and CEO of Carisma Therapeutics. "We are advancing on multiple fronts. We expect to report initial data from the Phase 1 study of CT-0525 in the first quarter of 2025. We also recently nominated our first development candidate in hepatocellular carcinoma with Moderna and are excited to bring additional in vivo CAR-M therapies forward, including autoimmune targets. Our liver fibrosis program is progressing as well, with the nomination of a development candidate anticipated in the first quarter of 2025. These key milestones move us closer to delivering transformative treatments for patients in need."

Third Quarter 2024 Highlights and Upcoming Milestones

Ex Vivo Oncology

· CT-0525 (Anti-HER2 chimeric antigen receptor monocyte (CAR-Monocyte))

o On November 5, 2024, Carisma announced the upcoming presentation of a trial in progress (TIP) poster for its Phase 1 clinical trial evaluating CT-0525, an autologous CAR-Monocyte therapy for the treatment of HER2+ solid tumors. The poster will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting in Houston, Texas, on November 8, 2024.

o In September 2024, Carisma submitted a protocol amendment for its Phase 1 study of CT-0525 to allow for the expansion of the study to include repeat dosing (up to two billion CAR positive cells administered every three weeks for up to five cycles) in combination with pembrolizumab, bolus dosing (up to10 billion CAR positive cells in a single dose) in combination with pembrolizumab, or either of these two dosing schedules as monotherapy (without checkpoint inhibitor). Repeat dosing in combination with pembrolizumab will be prioritized and the other three study arms may be activated as data indicates.

o Carisma expects to report initial data for Cohorts 1 and 2 of its Phase 1 study of CT-0525 in the first quarter of 2025.

In Vivo Program (Moderna Collaboration)

· Autoimmune disease (CAR-M + mRNA/LNP)

o On September 10, 2024, Carisma announced the expansion of its in vivo chimeric antigen receptor macrophage and monocyte ("CAR-M") collaboration with Moderna, Inc. ("Moderna") to include the nomination of two research targets for the treatment of autoimmune diseases. Carisma retains all rights in autoimmune disease beyond the two nominated targets, which will be exclusively partnered with Moderna.

· GPC3+ solid tumors (CAR-M + mRNA/LNP)

o On November 5, 2024, Carisma announced the upcoming presentation of new pre-clinical data for its anti-GPC3 in vivo CAR-M therapy for the treatment of hepatocellular carcinoma (HCC), developed in collaboration with Moderna. These data will be presented in a poster session at the SITC (Free SITC Whitepaper) Annual Meeting in Houston, Texas, on November 8, 2024. These preclinical data demonstrate robust anti-tumor activity and introduce a novel, off-the-shelf approach for GPC3+ solid tumors.

Fibrosis

o On August 6, 2024, Carisma announced that new preclinical data for liver fibrosis will be highlighted in a poster presentation at the American Association for the Study of Liver Diseases (AASLD) – The Liver Meeting 2024, to be held November 15 through 19, 2024, in San Diego, California.

o Carisma expects to nominate a development candidate for its liver fibrosis program in the first quarter of 2025.

Corporate Update

· On October 30, 2024, Carisma announced the appointment of Sohanya Cheng to the Board of Directors of the Company, effective October 31, 2024. Ms. Cheng brings over 20 years of experience in biopharmaceutical commercialization and research, with a strong focus on oncology. The Company concurrently announced the resignation of Michael Torok from Carisma’s Board of Directors, also effective October 31, 2024.

Third Quarter 2024 Financial Results

· Cash and cash equivalents as of September 30, 2024, were $26.9 million, compared to $40.4 million as of June 30, 2024.

· Research and development expenses for the three months ended September 30, 2024 were $11.3 million, compared to $19.6 million for the three months ended September 30, 2023. The decrease of $8.3 million was primarily due to implementation of our revised operating plan in the second quarter of 2024 in which we halted further development of CT-0508, paused development of CT-1119 and implemented a workforce reduction. As result of the revised operating plan, we experienced a decrease of $2.4 million related to halting development of CT-0508 and a $0.1 million decrease from pausing the development of CT-1119. In addition, the implementation of the revised operating plan resulted in a decrease in facilities and other expenses of $3.1 million due to less laboratory supplies and laboratory space needs and a $0.9 million decrease in direct personnel costs due to a reduction in headcount. Further, we experienced a $0.9 million decrease in direct costs associated with pre-clinical development of CT-0525 due to the timing of the development program and a decrease of $0.9 million in other clinical and pre-clinical development expenses resulting from the timing of certain studies in our in vivo collaboration with Moderna.

· General and administrative expenses for the three months ended September 30, 2024 were $5.2 million, compared to $6.6 million for the three months ended September 30, 2023. The decrease of $1.4 million was primarily due to our revised operating plan in which we recognized a $1.3 million decrease in professional fees as a result of our patent portfolio and expanding infrastructure in 2023, a $0.3 million decrease in facilities and supplies due to a decrease in office expenditures, a $0.2 million decrease in insurance costs, and a $0.1 million decrease in other expenses related to a decline in travel costs, partially offset by a $0.5 million increase in personnel costs driven by an increase in stock-based compensation.

· Net loss was $12.7 million for the third quarter of 2024, compared to a $21.4 million net loss for the same period in 2023.

Outlook

Carisma anticipates that its cash and cash equivalents of $26.9 million as of September 30, 2024 are sufficient to sustain its planned operations into the third quarter of 2025. The Company’s cash forecast contains estimates and assumptions, and management cannot predict the timing of all cash receipts and expenditures with certainty. Variances from management’s estimates and assumptions could impact the Company’s liquidity prior to the third quarter of 2025.

About CT-0525

CT-0525 is a first-in-class, ex vivo gene-modified autologous chimeric antigen receptor-monocyte (CAR-Monocyte) cellular therapy intended to treat solid tumors that overexpress human epidermal growth factor receptor 2 (HER2). It is being studied in a multi-center, open label, Phase 1 clinical trial for patients with advanced/metastatic HER2-overexpressing solid tumors that have progressed on available therapies. The CAR-Monocyte approach has the potential to address some of the challenges of treating solid tumors with cell therapies, including tumor infiltration, immunosuppression within the tumor microenvironment, and antigen heterogeneity. CT-0525 has the potential to enable significant dose escalation, enhance tumor infiltration, increase persistence, and reduce manufacturing time compared to macrophage therapy.

On November 7, 2024 cTRL Therapeutics, a biotechnology company advancing next-generation cell therapies for solid tumors, reported that it will present new data at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting 2024, taking place November 6-10 in Houston, TX (Press release, CTRL Therapeutics, NOV 7, 2024, View Source [SID1234647983]). The company will showcase two poster presentations that underscore the therapeutic potential of circulating tumor-reactive lymphocytes (cTRLs), enabled by the company’s proprietary IsoQore cell isolation platform.

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"We are excited to present data that demonstrate the robust tumor reactivity and therapeutic potential of cTRLs in patients with limited treatment options," said Ruben Rodriguez, PhD, Head of Research at cTRL Therapeutics. "These findings highlight the potential of our IsoQore platform to unlock the therapeutic use of cTRLs, previously thought to be impossible, offering a new way forward for patients with solid tumors."

Poster Presentations:

Abstract 401: Anti-tumor activity of circulating tumor-reactive lymphocytes (cTRLs) isolated from checkpoint-refractory melanoma patients that failed TIL manufacturing.
This poster will present data on cTRLs isolated from melanoma patients who had failed conventional TIL manufacturing. The results demonstrate strong tumor reactivity in cTRLs, with higher frequency of tumor-reactive TCR repertoire compared to TILs, providing a more potent anti-tumor response. The data underscore the potential of cTRLs as a simpler and more effective alternative to traditional cell therapy approaches like TIL therapy.
Poster Presentation: Friday, Nov. 8

Abstract 400: Circulating tumor-reactive lymphocytes (cTRLs) isolated from colorectal cancer (CRC) patients are reactive against autologous tumors and show less exhaustion than tumor-infiltrating lymphocytes (TILs).
This presentation highlights the potential of cTRLs isolated from CRC patients to outperform TILs. The data show that cTRLs exhibit lower levels of exhaustion markers (PD-1, CD39) and higher expression of memory/activation markers (CD27, CD28) and improved functionality and tumor reactivity compared to paired TILs. These findings position cTRLs as a promising new polyclonal T-cell therapy, eliminating the need for surgical tumor resection and expanding patient eligibility.
Poster Presentation: Saturday, Nov. 9
"These data highlight the strong potential of cTRLs as a next-generation approach in cell therapy," said Derrell Porter, M.D., CEO of CTRL Therapeutics. "With a non-invasive blood draw instead of surgical resection, and superior cell fitness compared to traditional cell therapies, cTRLs could offer patients a more accessible, scalable, and effective treatment option. We look forward to sharing these findings with the scientific community at SITC (Free SITC Whitepaper)."

cTRL Therapeutics continues to advance its proprietary IsoQore platform, which isolates and expands high-quality cTRLs from peripheral blood, paving the way for a new era of cell therapies that address key limitations of current modalities.