On December 12, 2024 Repare Therapeutics Inc. ("Repare" or the "Company") (Nasdaq: RPTX), a leading clinical-stage precision oncology company, reported positive data from its MYTHIC Phase 1 gynecologic expansion clinical trial evaluating the combination of lunresertib and camonsertib (Lunre+Camo) at the recommended Phase 2 dose (RP2D) in patients with endometrial cancer and platinum-resistant ovarian cancer (PROC) harboring lunre-sensitizing biomarkers (Press release, Repare Therapeutics, DEC 12, 2024, View Source [SID1234649081]).

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!

Lunresertib is a first-in-class precision oncology small molecule PKMYT1 inhibitor which targets cell cycle regulation in Lunre BM+ tumors (CCNE1 amplifications or FBXW7 or PPP2R1A deleterious alterations). Camonsertib is a potential best-in-class oral small molecule inhibitor of ATR, a critical component of the DNA damage response pathway.

"We are encouraged by the strong response and the clear benefit we observed in patients with endometrial and platinum-resistant ovarian cancers in the MYTHIC clinical trial," said Lloyd M. Segal, President and Chief Executive Officer of Repare. "These patients need new treatment options and our results support the potential for Lunre+Camo to make a real, positive difference if approved, particularly as a chemotherapy alternative. We have positive feedback from regulatory agencies in both the US and Europe and we look forward to getting started on a registrational Phase 3 trial of Lunre+Camo in endometrial cancer in the second half of 2025."

The MYTHIC clinical trial (NCT04855656) is a first-in-human, global, open-label Phase 1 dose-escalation clinical trial to evaluate safety, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of Lunre+Camo in patients with advanced solid tumors. As of the data cut-off date of November 14, 2024, 51 evaluable patients were enrolled in the gynecologic cancer expansion cohort of the MYTHIC trial.

Across all tumor types treated at the optimized RP2D (n=67), Lunre+Camo therapy demonstrated a favorable and differentiated tolerability profile when compared to current and emerging therapies. The most common adverse event was anemia (26.9%, Grade 3).

Key Cohort Clinical Findings

Endometrial Cancer Patients:

The 27 evaluable patients with endometrial cancer had a median age of 67 years. All patients exhibited high-risk profiles:

•
100% of patients have undergone prior platinum therapy

•
77.8% of patients received immune checkpoint inhibitors

•
59% of patients received the combination as a fourth line of therapy or beyond

•
18.5% of patients had carcinosarcoma

•
85% of tumors had p53 mutations

•
No tumors with microsatellite instability (MSI)-high status were enrolled indicating proficient mismatch repair (pMMR) status
•
Within the Lunre BM+ subset: 56% of tumors had PPP2R1A mutations; 22% carried FBXW7 mutations; 15% had CCNE1 amplification; and 7% of tumors had multiple mutations

Key efficacy outcomes in evaluable patients with endometrial cancer (N=27):

•
ORR was 25.9% (confirmed ORR in 5 out of 7 patients)

•
Clinical benefit was observed in 48.1% of patients, with responses frequently occurring after 12 weeks or more

•
At the 24-week landmark analysis, nearly half of patients experienced durable clinical benefit (24-week PFS [PFS24w] = 43% [95% CI, 21-63%])

Platinum-Resistant Ovarian Cancer Patients:

The 24 evaluable patients with PROC had a median age of 63 years. All patients exhibited high-risk profiles:

•
100% of patients were platinum-resistant or platinum ineligible

•
45.8% of patients had received prior PARP inhibitors

•
70.8% of patients had received prior bevacizumab

•
54% of patients received the combination as a fourth line of therapy or beyond

•
100% of tumors had p53 mutations

•
Within the Lunre BM+ subset: 87.5% of tumors had CCNE1 amplification; 4.2% had FBXW7 mutations; 4.2% had PPP2R1A mutations; and 4.2% of tumors had multiple mutations

Key efficacy outcomes in evaluable patients with PROC (N=24):

•
ORR was 37.5% (confirmed ORR in 4 out of 9 patients)

•
Clinical benefit was observed in 79% of patients

•
PFS at the 24-week landmark analysis was (PFS24w = 45% [95% CI, 22-66%]).

"Those patients with recurrent gynecologic cancers have limited treatment options as tumors often become resistant to standard of care therapy," said Brian Slomovitz, MD, MS, FACOG, Director, Gynecologic Oncology, Co-chair of the Cancer Research Center, Mount Sinai Medical Center. "They urgently need new treatment options. Repare’s differentiated, biomarker-driven approach addresses this population and may offer a solution. These data support the potential of Lunre+Camo as a new treatment option to fill this unmet need for patients with endometrial and platinum-resistant ovarian cancers."

Repare has consulted with both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency, who have provided guidance into the Company’s registrational development plans for Lunre+Camo in gynecologic tumors, including assessment of the contribution of components, dose and schedule and preliminary alignment on the proposed registrational development approach. Repare plans to provide the final Phase 3 trial protocols for regulatory clearance imminently and intends to start the first Phase 3 Lunre+Camo trial in endometrial cancer in the second half of 2025. Additionally, the Company expects to initiate a small contribution of components trial in up to 40 patients with endometrial cancer in the first quarter of 2025.

"The results of the MYTHIC clinical trial increase our confidence in the potential to bring Lunre+Camo to patients living with this aggressive subset of recurrent endometrial cancer," said Maria Koehler, MD, PhD, Chief Medical Officer of Repare. "We are deeply grateful to the patients and investigators who participated in this trial, and we look forward to building on these promising data through the registrational clinical trials using Lunre+Camo as a potential new standard of care for those patients, if approved."

Conference Call and Webcast:

Repare will host a conference call and webcast today, December 12, at 4:30 p.m. ET to discuss the results. Repare’s executive management team will be joined by Brian Slomovitz, MD, MS, FACOG, Director, Gynecologic Oncology, Co-chair of the Cancer Research Center, Mount Sinai Medical Center.

To access the call, please dial (646) 357-8785 (U.S. and Canada) or (800) 836-8184 (international) at least 10 minutes prior to the start time and ask to be joined to the Repare Therapeutics call. A live webcast and presentation materials will be available in the Investor section of the Company’s website at View Source A webcast replay will also be archived for at least 30 days.

On December 12, 2024 Synaffix B.V., a Lonza company (SIX:LONN) focused on commercializing its clinical-stage platform technology for the development of antibody-drug conjugates (ADCs) with best-in-class therapeutic index, reported that it has entered into a licensing agreement with Elevation Oncology, Inc. (Nasdaq: ELEV), an innovative oncology company focused on the discovery and development of selective cancer therapies to treat patients across a range of solid tumors with significant unmet medical needs (Press release, Synaffix, DEC 12, 2024, View Source [SID1234649080]).

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!

Synaffix gives Elevation Oncology global access to its clinical stage, site-specific ADC technology platform, including GlycoConnect antibody conjugation technology, HydraSpace polar spacer technology, as well as the toxSYN linker-payload, SYNstatin E, which enables the transformation of Elevation Oncology’s antibody into a differentiated ADC with best-in-class potential.

Under the terms of the agreement, Synaffix is eligible to receive up to USD 368 million in upfront and clinical, regulatory, and commercial milestone payments, plus tiered royalties on net sales. Synaffix is responsible for manufacturing the components related to its proprietary technologies, and Elevation Oncology is responsible for the research, development, manufacturing, and commercialization of the ADC.

Peter van de Sande, Head of Synaffix, said: "As a dedicated partner in the ADC space, Synaffix is excited to collaborate with Elevation Oncology to push the boundary of ADC innovation. With our state-of-the-art ADC technology platform and established supply chain, Elevation is well-positioned to accelerate the development of its differentiated HER3 ADC."

David Dornan, Chief Scientific Officer at Elevation Oncology, commented: "Our partnership with Synaffix enables us to build a HER3 ADC candidate with best-in-class potential, which leverages Synaffix’s state-of-the-art site-specific conjugation and differentiated linker-payload for a potentially improved safety and efficacy profile. We look forward to advancing our pipeline as we work toward transforming the care and treatment of patients living with solid tumors that express HER3."

On December 12, 2024 Pfizer Inc. (NYSE:PFE) and Alliance Foundation Trials, LLC (AFT) reported results from the Phase 3 PATINA trial demonstrating that the addition of IBRANCE (palbociclib) to current standard-of-care first-line maintenance therapy (following induction chemotherapy) resulted in statistically significant and clinically meaningful improvement in progression-free survival (PFS) by investigator assessment in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) (Press release, Seagen, DEC 12, 2024, View Source [SID1234649079]). In the study, which is sponsored by AFT, median PFS was 44.3 months (95% CI: 32.4-60.9) for patients treated with IBRANCE in combination with anti-HER2 therapy (trastuzumab or trastuzumab plus pertuzumab) and endocrine therapy, and 29.1 months (95% CI: 23.3-38.6) for patients treated with anti-HER2 therapy and endocrine therapy alone [HR: 0.74 (95% CI, 0.58-0.94); unstratified 1-sided p= 0.0074]. This represents an extension in median PFS of over 15 months. Overall survival, a secondary endpoint, was not yet mature at the time of the analysis. These results are being presented during a late-breaking oral session (Abstract GS2-12) and highlighted in the press program at the 47th San Antonio Breast Cancer Symposium (SABCS) in San Antonio, Texas.

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!

"PATINA is the first large Phase 3 study to show the benefit of CDK4/6 inhibition in HR-positive, HER2-positive metastatic breast cancer," said Otto Metzger, M.D., principal investigator of the trial for Alliance Foundation Trials and Medical Oncologist at the Dana-Farber Cancer Institute. "These results support the potential of this maintenance treatment to slow disease progression and improve clinical outcomes in this patient population."

Approximately 10% of all breast cancers are HR+, HER2+i , which is sometimes referred to as double-positive or triple-positive breast cancer. Despite advances in treatment, the development of resistance to anti-HER2 and endocrine therapy is a challenge, and novel therapeutic approaches are needed for HR+, HER2+ MBC.ii IBRANCE is not currently indicated for HR+, HER2+ MBC.

"IBRANCE, the first CDK4/6 inhibitor, revolutionized the treatment of HR-positive, HER2-negative metastatic breast cancer, and has been prescribed to over 773,000 patients since its initial approval in 2015," said Roger Dansey, M.D., Chief Development Officer, Oncology, Pfizer. "These results demonstrate that the addition of IBRANCE to standard of care shows promise as maintenance therapy in HR-positive, HER2-positive disease. PATINA underscores Pfizer’s ongoing commitment to addressing the unmet needs of people with breast cancer, and we look forward to discussing the results with regulatory authorities."

The safety and tolerability of IBRANCE in the PATINA study was consistent with its known safety profile in HR+, human epidermal growth factor receptor 2-negative (HER2-) MBC, and no new safety signals were identified. The most common adverse events observed with IBRANCE were hematologic toxicities, such as neutropenia and leukopenia. Non-hematologic adverse events included fatigue, stomatitis and diarrhea, which were generally mild to moderate in severity.

Since its initial regulatory approval in 2015, IBRANCE continues to be a standard-of-care first-line treatment for HR+, HER2- MBC and has been approved in more than 108 countries. Pfizer plans to share the results from PATINA with regulatory authorities.

About the PATINA Trial
PATINA (AFT-38) is a randomized, open-label Phase 3 study to evaluate the efficacy and safety of IBRANCE (palbociclib) in combination with anti-HER2 therapy (trastuzumab or trastuzumab plus pertuzumab) and endocrine therapy compared to anti-HER2 therapy and endocrine therapy alone as a first-line maintenance therapy (following induction chemotherapy treatment) for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC). While Pfizer is providing funding support for the trial, PATINA is sponsored by Alliance Foundation Trials, LLC (AFT) in collaboration with six international cancer research groups in the U.S., Germany, Italy, Spain, Australia, and New Zealand.

Study participants who were previously treated with anti-HER2 therapy were randomized to receive IBRANCE, in addition to anti-HER2 therapy and endocrine therapy (n=261), or anti-HER2 therapy and endocrine therapy alone (n=257). The primary endpoint is progression-free survival (PFS) as assessed by the investigator. Overall survival is a secondary endpoint.

About IBRANCE (palbociclib)
IBRANCE is an oral inhibitor of CDKs 4 and 6,iii which are key regulators of the cell cycle that trigger cellular progression.iv,v In the U.S., IBRANCE is indicated for the treatment of adult patients with HR+, HER2- advanced or metastatic breast cancer in combination with an aromatase inhibitor as initial endocrine-based therapy in postmenopausal women or in men; or with fulvestrant in patients with disease progression following endocrine therapy.

The full U.S. Prescribing Information for the IBRANCE tablets and the IBRANCE capsules can be found here and here.

IMPORTANT IBRANCE (palbociclib) SAFETY INFORMATION FROM THE U.S. PRESCRIBING INFORMATION
Neutropenia was the most frequently reported adverse reaction in PALOMA-2 (80%) and PALOMA-3 (83%). In PALOMA-2, Grade 3 (56%) or 4 (10%) decreased neutrophil counts were reported in patients receiving IBRANCE plus letrozole. In PALOMA-3, Grade 3 (55%) or Grade 4 (11%) decreased neutrophil counts were reported in patients receiving IBRANCE plus fulvestrant. Febrile neutropenia has been reported in 1.8% of patients exposed to IBRANCE across PALOMA-2 and PALOMA-3. One death due to neutropenic sepsis was observed in PALOMA-3. Inform patients to promptly report any fever.

Monitor complete blood count prior to starting IBRANCE, at the beginning of each cycle, on Day 15 of first 2 cycles and as clinically indicated. Dose interruption, dose reduction, or delay in starting treatment cycles is recommended for patients who develop Grade 3 or 4 neutropenia.

Severe, life-threatening, or fatal interstitial lung disease (ILD) and/or pneumonitis can occur in patients treated with CDK4/6 inhibitors, including IBRANCE when taken in combination with endocrine therapy. Across clinical trials (PALOMA-1, PALOMA-2, PALOMA-3), 1.0% of IBRANCE-treated patients had ILD/pneumonitis of any grade, 0.1% had Grade 3 or 4, and no fatal cases were reported. Additional cases of ILD/pneumonitis have been observed in the post-marketing setting, with fatalities reported.

Monitor patients for pulmonary symptoms indicative of ILD/pneumonitis (e.g., hypoxia, cough, dyspnea). In patients who have new or worsening respiratory symptoms and are suspected to have developed pneumonitis, interrupt IBRANCE immediately and evaluate the patient. Permanently discontinue IBRANCE in patients with severe ILD or pneumonitis.

Based on the mechanism of action, IBRANCE can cause fetal harm. Advise females of reproductive potential to use effective contraception during IBRANCE treatment and for at least 3 weeks after the last dose. IBRANCE may impair fertility in males and has the potential to cause genotoxicity. Advise male patients to consider sperm preservation before taking IBRANCE. Advise male patients with female partners of reproductive potential to use effective contraception during IBRANCE treatment and for 3 months after the last dose. Advise females to inform their healthcare provider of a known or suspected pregnancy. Advise women not to breastfeed during IBRANCE treatment and for 3 weeks after the last dose because of the potential for serious adverse reactions in nursing infants.

The most common adverse reactions (≥10%) of any grade reported in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were neutropenia (80% vs 6%), infections (60% vs 42%), leukopenia (39% vs 2%), fatigue (37% vs 28%), nausea (35% vs 26%), alopecia (33% vs 16%), stomatitis (30% vs 14%), diarrhea (26% vs 19%), anemia (24% vs 9%), rash (18% vs 12%), asthenia (17% vs 12%), thrombocytopenia (16% vs 1%), vomiting (16% vs 17%), decreased appetite (15% vs 9%), dry skin (12% vs 6%), pyrexia (12% vs 9%), and dysgeusia (10% vs 5%).

The most frequently reported Grade ≥3 adverse reactions (≥5%) in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were neutropenia (66% vs 2%), leukopenia (25% vs 0%), infections (7% vs 3%), and anemia (5% vs 2%).

Lab abnormalities of any grade occurring in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were decreased WBC (97% vs 25%), decreased neutrophils (95% vs 20%), anemia (78% vs 42%), decreased platelets (63% vs 14%), increased aspartate aminotransferase (52% vs 34%), and increased alanine aminotransferase (43% vs 30%).

The most common adverse reactions (≥10%) of any grade reported in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were neutropenia (83% vs 4%), leukopenia (53% vs 5%), infections (47% vs 31%), fatigue (41% vs 29%), nausea (34% vs 28%), anemia (30% vs 13%), stomatitis (28% vs 13%), diarrhea (24% vs 19%), thrombocytopenia (23% vs 0%), vomiting (19% vs 15%), alopecia (18% vs 6%), rash (17% vs 6%), decreased appetite (16% vs 8%), and pyrexia (13% vs 5%).

The most frequently reported Grade ≥3 adverse reactions (≥5%) in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were neutropenia (66% vs 1%) and leukopenia (31% vs 2%).

Lab abnormalities of any grade occurring in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were decreased WBC (99% vs 26%), decreased neutrophils (96% vs 14%), anemia (78% vs 40%), decreased platelets (62% vs 10%), increased aspartate aminotransferase (43% vs 48%), and increased alanine aminotransferase (36% vs 34%).

Avoid concurrent use of strong CYP3A inhibitors. If patients must be administered a strong CYP3A inhibitor, reduce the IBRANCE dose to 75 mg. If the strong inhibitor is discontinued, increase the IBRANCE dose (after 3-5 half-lives of the inhibitor) to the dose used prior to the initiation of the strong CYP3A inhibitor. Grapefruit or grapefruit juice may increase plasma concentrations of IBRANCE and should be avoided. Avoid concomitant use of strong CYP3A inducers. The dose of sensitive CYP3A substrates with a narrow therapeutic index may need to be reduced as IBRANCE may increase their exposure.

For patients with severe hepatic impairment (Child-Pugh class C), the recommended dose of IBRANCE is 75 mg. The pharmacokinetics of IBRANCE have not been studied in patients requiring hemodialysis.

On December 12, 2024 Kiromic BioPharma, Inc. (OTCQB: KRBP) ("Kiromic" or the "Company") reported favorable ongoing efficacy results from the eight-month follow-up visit for the fourth patient enrolled in its Deltacel-01 Phase 1 clinical trial, and provides additional updates on the first and seventh patients (Press release, Kiromic, DEC 12, 2024, View Source [SID1234649077]). This trial is evaluating Deltacel (KB-GDT-01), the Company’s allogeneic, off-the-shelf, Gamma Delta T-cell (GDT) therapy, in patients with stage 4 metastatic non-small cell lung cancer (NSCLC) who have failed to respond to standard therapies.

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!

8-Month Follow-Up for Patient #4: Partial Response with Tumor Reduction of 32%

Preliminary results from the eight-month follow-up visit for the fourth patient enrolled in Deltacel-01 revealed an approximately 32% decrease in tumor volume compared with the pre-treatment size. This patient continues to experience clinical benefit without adverse events.

11-Month Follow-Up for Patient #1: Stable Disease Maintained

The first patient enrolled in the Deltacel-01 trial has maintained stable disease with no evidence of disease progression or new sites of malignancy. Kiromic last reported that in this patient, the tumor size was reduced by approximately 27% compared with the pre-treatment size, and no new sites of disease were identified. As a result, the PFS has reached 11 months with no reported adverse events. This patient’s final follow-up visit is scheduled for the end of December.

Patient #7 Completes Treatment

The seventh patient successfully completed the Deltacel-01 treatment regimen and is tolerating therapy well. Initial efficacy results for this patient are expected in early January 2025.

Patient #8 Enrolled

The eighth patient in the Deltacel-01 clinical study was enrolled this week at the Clinical Research Advisors Koreatown, a satellite location of the Beverly Hills Cancer Center (BHCC).

"The magnitude of the tumor reduction observed in Patient #4 is significant and highly encouraging. We look forward to reporting results from the first and seventh patients in January, and expect to enroll additional patients through the beginning of 2025," said Pietro Bersani, Chief Executive Officer of Kiromic BioPharma.

"The remarkable 32% tumor reduction seen in the fourth patient treated with Deltacel is truly exciting and holds great promise for improving outcomes for patients with advanced lung cancer. As a leading cancer center focused on delivering the most innovative and effective therapies, we are proud to partner with Kiromic on this important clinical trial. The early safety and tolerability data, coupled with these signs of robust antitumor activity, suggest Deltacel’s promise as a transformative new treatment option. We look forward to continued enrollment and results that could change the standard of care for these patients who have exhausted other options," said Dr. Afshin Eli Gabayan, Medical Oncologist, Medical Director, and Principal Investigator at Beverly Hills Cancer Center. "At the Beverly Hills Cancer Center, our mission is to provide our patients with access to the most advanced and cutting-edge cancer treatments available. By working with visionary companies like Kiromic, we are able to offer our patients the opportunity to participate in groundbreaking clinical trials that have the potential to transform cancer care. We look forward to continuing to support the Deltacel-01 trial and reporting on the progress of the additional patients enrolled at our center. Together, we are making important strides in the fight against this devastating disease."

About Deltacel-01

In Kiromic’s open-label Phase 1 clinical trial, titled "Phase 1 Trial Evaluating the Safety and Tolerability of Gamma Delta T Cell Infusions in Combination With Low Dose Radiotherapy in Subjects With Stage 4 Metastatic Non-Small Cell Lung Cancer" (NCT06069570), patients with stage 4 NSCLC will receive two intravenous infusions of Deltacel with four courses of low-dose, localized radiation over a 10-day period. The primary objective of Deltacel-01 is to evaluate safety, while secondary measurements include objective response, progression-free survival, overall survival, time to progression, time to treatment response and disease control rates.

About Deltacel

Deltacel (KB-GDT-01) is an investigational gamma delta T-cell (GDT) therapy currently in the Deltacel-01 Phase 1 trial for the treatment of stage 4 metastatic NSCLC. An allogeneic product consisting of unmodified, donor-derived gamma delta T cells, Deltacel is the leading candidate in Kiromic’s GDT platform. Deltacel is designed to exploit the natural potency of GDT cells to target solid cancers, with an initial clinical focus on NSCLC, which represents about 80% to 85% of all lung cancer cases. Data from two preclinical studies demonstrated Deltacel’s favorable safety and efficacy profile when it was combined with low-dose radiation.

On December 12, 2024 TuHURA Biosciences, Inc. (Nasdaq: HURA) ("TuHURA"), a Phase 3 registration-stage immune-oncology company developing novel technologies to overcome resistance to cancer immunotherapy, and Kineta, Inc. (OTC Pink: KANT) ("Kineta"), a clinical-stage biotechnology company focused on the development of novel immunotherapies in oncology that address cancer immune resistance, reported that they have entered into a definitive merger agreement in which TuHURA would acquire Kineta, including the rights to Kineta’s novel KVA12123 antibody, for a combination of cash and shares of TuHURA common stock via a merger transaction (the "Proposed Transaction") (Press release, Kineta, DEC 12, 2024, View Source;utm_medium=rss&utm_campaign=tuhura-biosciences-inc-enters-into-definitive-merger-agreement-to-acquire-kineta-inc [SID1234649076]).

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!

"We are pleased to have entered into this definitive agreement with Kineta, which represents the culmination of the Exclusivity and Right of First Offer Agreement that TuHURA and Kineta entered into in July 2024. Our strategy of providing Kineta this past summer with a $5 million exclusivity fee to restart and finish their Phase 1 monotherapy and combination with pembrolizumab trial demonstrated our view that the PK/PD profile would position KVA12123 as a potential best-in-class V-domain Ig suppressor of T-cell activation (VISTA)-inhibiting antibody. We believe the real potential for this class of checkpoint inhibitors resides in the treatment of blood related cancers. The data presented at the December 2024 ASH (Free ASH Whitepaper) meeting indicates a strong correlation between NPM1 mutations (mNPM1) and elevated VISTA expression, particularly in the context of acute myeloid leukemia (AML), where high VISTA levels on leukemia cells, associated with mNPM1, can potentially contribute to immune evasion and disease progression impacting their treatment response. Given mNPM1 drives leukemogenesis through menin, and the introduction of menin inhibitors improving treatment responses in mNPM1-associated AML, a combination with a VISTA-inhibiting antibody could be the next step in improving response rates in AML," commented James Bianco, M.D., President and Chief Executive Officer of TuHURA.

KVA12123 is a VISTA-blocking immunotherapy in development as a monoclonal antibody infusion drug dosed every two-week cycles. It is completing two clinical trials both as a monotherapy and in combination with Merck’s anti-PD1 therapy, KEYTRUDA (pembrolizumab), in patients with advanced treatment-refractory solid tumors. Competitive therapies targeting VISTA have demonstrated either poor monotherapy anti-tumor activity in preclinical models or induction of cytokine release syndrome (CRS) in human clinical trials. Through the combination of unique epitope binding and an optimized IgG1 Fc region, KVA12123 demonstrates strong monotherapy tumor growth inhibition in preclinical models without evidence of CRS in clinical trial participants. KVA12123 has been shown to de-risk the VISTA target and provides a novel approach to address immune suppression in the tumor microenvironment (TME) with a mechanism of action that is differentiated and complementary with T cell focused therapies. KVA12123 may be an effective immunotherapy for many types of cancer and represents the introduction of a new class of checkpoint inhibitors.

VISTA is a negative immune checkpoint that suppresses T cell function in a variety of solid tumors. High VISTA expression in tumor correlates with poor survival in cancer patients and has been associated with a lack of response to other immune checkpoint inhibitors. Blocking VISTA induces an efficient polyfunctional immune response to address immunosuppression and drives anti-tumor responses.

KVA12123 has completed enrollment in its monotherapy arm, demonstrating safety at its highest dose level (1000mg). Kineta anticipates completion of enrollment in the combination therapy arm where KVA12123 is administered with Merck’s anti-PD1 therapy, KEYTRUDA (pembrolizumab). Initial results were reported earlier this year at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024 and at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) meeting, supporting best-in-class profile.

"Following a thorough review of exploring strategic alternatives for Kineta and the discussions held with TuHURA over the course of the past several months, we believe this acquisition by TuHURA maximizes shareholder value and provides an exciting development path forward for KVA12123. We believe KVA12123 has multiple synergies with both of TuHURA’s IFx and Delta receptor antibody-drug conjugate (ADC) and peptide drug conjugate (PDC) technologies and that a TuHURA acquisition will provide the necessary resources to advance KVA12123 through its clinical development, maximizing value for Kineta’s shareholders," said Craig W. Philips, President of Kineta. "In addition to the TuHURA transaction, Kineta is continuing to pursue partnership opportunities for some of its other non-KVA12123-related products and technologies prior to the close of the TuHURA transaction."

About the Proposed Transaction
Under the terms of the merger agreement, upon the completion of the Proposed Transaction, Kineta stockholders will receive their pro rata share (based on the number of Kineta fully diluted shares held by them) of aggregate merger consideration consisting of a combination of cash and shares of TuHURA common stock. The cash component of the aggregate merger consideration will be a base cash amount of $9,005,000 (consisting of a value of $15,000,000 minus the $5,995,000 advanced to Kineta under the Exclusivity and Right of First Offer Agreement) less the sum of Kineta’s working capital deficit at the closing of the Proposed Transaction and any working capital loans made by TuHURA to Kineta between the signing of the merger agreement and closing of the Proposed Transaction. The share component of the aggregate merger consideration will consist of an aggregate of up to approximately 3,476,568 shares of TuHURA common stock, subject to a six-month holdback of approximately 869,142 of such shares to satisfy certain additional liabilities of the closing date that may be identified after the closing. As additional merger consideration, Kineta stockholders will be entitled to receive their pro rata share of certain payments that Kineta may receive after the closing from the potential pre-closing sale by Kineta of certain non-KVA12123 products and technologies.

In connection with the merger agreement, TuHURA and Kineta entered into a Clinical Trial Funding Agreement under which TuHURA agreed to continue to fund clinical trial expenses for KVA12123 in an amount of up to $900,000, which may be increased upon mutual agreement. The merger agreement also provides that Kineta may request the extension of up to $2,000,000 in working capital loans from TuHURA, $1,750,000 of which will be contingent on the completion of a financing transaction by TuHURA.

The merger agreement has been unanimously approved by the boards of directors of both companies and is subject to Kineta stockholder approval. The completion of the Proposed Transaction is also subject to the satisfaction or waiver of certain other conditions, such as the approval by TuHURA’s stockholders of an increase in the number of authorized shares of TuHURA common stock, Kineta’s working capital deficit not exceeding $12,000,000 at the time of closing, the effectiveness of a registration statement on Form S-4 registering the shares of TuHURA common stock issuable to the Kineta stockholders in the Proposed Transaction, and other customary closing conditions. The Proposed Transaction is currently expected to close in the first quarter of 2025.