On August 12, 2024 Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, reported financial results for the second quarter ended June 30, 2024 (Press release, Leap Therapeutics, AUG 12, 2024, View Source [SID1234645732]).

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!

Leap Highlights:

· Overall response rate (ORR) increases to 33% across all evaluable patients and 38% across evaluable patients with left-sided CRC in updated data from Part A of the Phase 2 DeFianCe study evaluating DKN-01 in combination with bevacizumab and chemotherapy in second-line patients with advanced colorectal cancer (CRC)
· Expanded the randomized controlled Part B of the DeFianCe study to 180 patients; enrollment expected to be completed by end of September 2024 with data expected in mid-2025
· Patient follow-up continues in the randomized controlled Part C of the Phase 2 DisTinGuish study evaluating DKN-01 in combination with tislelizumab and chemotherapy in first-line patients with advanced gastroesophageal junction (GEJ) and gastric cancer; data expected in Q4 2024 or early 2025
· Completed $40 million private placement with new and existing investors, including Gilead Sciences, Inc.

"With the momentum provided by our $40 million private placement, we are positioned to achieve our critical company milestones," said Douglas E. Onsi, President and Chief Executive Officer of Leap. "We have executed well on our two DKN-01 randomized controlled trials and on preparatory activities for registrational studies. We look forward to sharing initial data from both randomized controlled studies over the next 12 months as we strive to deliver new treatments for patients fighting against cancer."

DKN-01 Development Update

· ORR increases in updated data from Part A of the DeFianCe Study. The DeFianCe study (NCT05480306) is a Phase 2 study evaluating DKN-01 in combination with bevacizumab and chemotherapy in second-line patients with advanced microsatellite stable CRC. Preliminary results from Part A of the study were previously reported at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium in January 2024. In April 2024, a ninth Part A patient was identified as having a partial response (PR). This patient, who has left-sided Consensus Molecular Subtype 4 CRC with APC and TP53 mutations and KRAS wildtype genetics, had been previously treated with cetuximab and chemotherapy. The patient enrolled in Part A in March 2023 and had a best response of stable disease (SD) for over a year before the tumor reduction deepened into a PR. The patient remains on study with a confirmed PR.

· Key Updated Part A Findings (as of June 7, 2024 data cut-off):

o Across all patients enrolled (n=33):

§ ORR among response-evaluable patients (n=27) was 33% and disease control rate (DCR) was 93%, including 9 PRs and 16 patients with a best response of SD
§ Median progression-free survival (PFS) was unchanged at 6.3 months

o Enhanced activity in patients with left-sided tumors (n=25), a group that has more frequent activation of the Wnt pathway modulated by DKK1

§ 38% ORR and 100% DCR in response-evaluable population (8 PRs, 13 SDs)
§ Median PFS was unchanged at 8.6 months

o DKN-01 plus bevacizumab and chemotherapy was well-tolerated, with a majority of DKN-01 related events being low grade (Grade 1/2)

· Enrollment in Part B of the DeFianCe Study in CRC patients is ongoing and expected to be completed by the end of September 2024. The Company expanded the randomized controlled Part B of the DeFianCe study from 130 to 180 patients and included PFS in the subpopulation of patients with left-sided CRC as an additional primary endpoint. As of August 9, 2024, 161 patients have enrolled in Part B. The Company expects to complete enrollment by the end of September 2024, with data expected mid-2025.

· Randomized controlled Part C of the DisTinGuish study in patients with GEJ and gastric cancer is ongoing, with initial data expected in Q4 2024 or early 2025. The DisTinGuish study (NCT0436380) is a Phase 2, randomized, open-label, multicenter study of DKN-01 in combination with tislelizumab and chemotherapy in first-line, HER-2 negative patients with GEJ and gastric cancer. Part C enrolled 170 patients randomized 1:1 to evaluate DKN-01 in combination with tislelizumab and chemotherapy, compared to tislelizumab and chemotherapy alone. The Company expects to report initial data from Part C of the DisTinGuish study in Q4 2024 or early 2025.

Business Update:

· Completed a $40 million private placement. In April 2024, Leap entered into a securities purchase agreement with a select group of new and existing investors including Gilead Sciences, Inc., a life sciences-focused investor, Samsara BioCapital, LP, 683 Capital Partners, LP, Laurion Capital Management LP, and Rock Springs Capital Management LP. Gross proceeds from the private placement were approximately $40 million. The net proceeds from this financing, combined with existing cash, cash equivalents and marketable securities, are expected to fund Leap’s operating and capital expenditures into the second quarter of 2026.

Selected Second Quarter 2024 Financial Results

Net Loss was $20.4 million for the second quarter 2024, compared to $13.4 million for the same period in 2023. The increase was primarily due to an increase in research and development expenses.

Research and development expenses were $17.9 million for the second quarter 2024, compared to $11.1 million for the same period in 2023. The increase of $6.8 million was primarily due to an increase of $5.7 million in clinical trial costs due to patient enrollment, the duration of patients on study, the enhancement of correlative studies, increase in site activity associated with Part C of the DisTinGuish study, and the expansion of the size of Part B of the DeFianCe study. There was also an increase of $0.6 million in manufacturing costs related to clinical trial material and manufacturing campaigns and an increase of $0.5 million in payroll and other related expenses due to an increase in headcount of our R&D full-time employees.

General and administrative expenses were $3.4 million for the second quarter 2024, compared to $3.6 million for the same period in 2023. The decrease was due to a decrease of $0.3 million in professional fees associated with our business development activities, partially offset by a $0.1 million increase in payroll and other related expenses.

Cash and cash equivalents totaled $78.5 million at June 30, 2024.

On August 12, 2024 Aethlon Medical, Inc. (NASDAQ: AEMD), a medical therapeutic company focused on developing products to treat cancer and life-threatening infectious diseases, reported that, on August 6, 2024, the Bellberry Human Research Ethics Committee (BHREC) granted full ethics approval to the Pindara Private Hospital for a safety, feasibility and dose-finding clinical trial of the Hemopurifier in patients with solid tumors who have stable or progressive disease during anti-PD-1 monotherapy treatment, such as Merck’s Keytruda (pembrolizumab) or Bristol Myers Squibb’s Opdivo (nivolumab) (AEMD-2022-06 Hemopurifier Study) (Press release, Aethlon Medical, AUG 12, 2024, View Source [SID1234645755]). The approval is valid for one year, until August 6, 2025. The trial will be conducted by Dr. Marco Matos and his staff at the Pindara Private Hospital, located in Queensland, Australia.

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 quite pleased that the BHREC accepted our responses to their thoughtful questions during their review and determined that our study meets the requirements of the National Statement application. Dr. Matos and his research team have a proven track record of enrollment in device trials in oncology patients that provides momentum to these trials," stated Steven LaRosa, MD, Chief Medical Officer of Aethlon Medical. "This is the second ethics committee approval we have received for our oncology trial in Australia after receiving approval from the ethics committee for Royal Adelaide Hospital in June."

Dr. LaRosa continued, "The next step is to receive approval from the Research Governance Office at each hospital which reviews indemnities and insurance. Once these approvals are obtained, Aethlon, in concert with our Australian Contract Research Organization, ReSQ, will conduct Site Initiation Visits (SIVs), after which patient enrollment may proceed."

Currently, only approximately 30% of cancer patients who receive pembrolizumab or nivolumab treatment for solid tumors will have lasting clinical responses to these agents. Extracellular vesicles (EVs) produced by tumors have been implicated in resistance to anti-PD-1 therapies as well as the spread of cancers. The Aethlon Hemopurifier has been designed to bind and remove these EVs from the bloodstream, which may improve therapeutic response rates to anti-PD-1 antibodies. In preclinical studies, the Hemopurifier has been shown to reduce the number of exosomes in cancer patient plasma samples.

The primary endpoint of the approximate nine to 18-patient, safety, feasibility and dose-finding trial is safety. The trial will monitor any adverse events and clinically significant changes in lab tests of Hemopurifier treated patients with solid tumors with stable or progressive disease at different treatment intervals, after a two-month run in period of PD-1 antibody, Keytruda or Opdivo monotherapy. Patients who do not respond to the PD-1 therapy will be eligible to enter the Hemopurifier period of the study, where sequential cohorts will receive 1, 2 or 3 Hemopurifier treatments during a one-week period. In addition to monitoring safety, the study is designed to examine the number of Hemopurifier treatments needed to decrease the concentration of EVs and if these changes in EV concentrations improve the body’s own natural ability to attack tumor cells. These exploratory central laboratory analyses are expected to inform the design of a subsequent efficacy and safety, Premarket Approval (PMA), study required by regulatory agencies.

On August 12, 2024 Marker Therapeutics, Inc. (Nasdaq: MRKR), a clinical-stage immuno-oncology company focusing on developing next-generation T cell-based immunotherapies for the treatment of hematological malignancies and solid tumor indications, reported that the Company has been awarded a $2 million grant from the National Institutes of Health (NIH) Small Business Innovation Research (SBIR) program to support the clinical investigation of MT-601 in patients with non-Hodgkin’s lymphoma (NHL) who have relapsed following anti-CD19 chimeric antigen receptor (CAR) T cell therapy (Press release, Marker Therapeutics, AUG 12, 2024, View Source [SID1234645733]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The SBIR grant has been awarded based in part on Marker’s preliminary clinical data in patients with lymphoma (Press Release, September 11, 2023) as well as non-clinical data demonstrating the anti-tumor activity of MT-601 on anti-CD19 CAR resistant lymphoma cells (Press Release, May 31, 2023). The proceeds of the grant will support the nationwide multi-center Phase 1 APOLLO study (ClinicalTrials.gov identifier: NCT05798897), evaluating the safety and efficacy of MT-601, a multi-tumor associated antigen (multiTAA)-specific T cell product, in patients with relapsed NHL including those previously treated with anti-CD19 CAR-T cell therapy. Including this SBIR grant, the Company has been awarded over $19 million in non-dilutive funding proceeds.

"We are pleased to receive the SBIR grant from the NIH to support our clinical Phase 1 study in CAR-relapsed patients with non-Hodgkin’s lymphoma," said Juan Vera, M.D., President and CEO of Marker Therapeutics. "Although anti-CD19 CAR-T cells are rapidly expanding as a treatment option in patients with hematological malignancies, approximately 40-60% of patients will relapse within the first year of therapy with currently no standard of care for patients post CD19-targeting CAR-T cells. The NIH award process is highly competitive, and we believe that the decision the NIH made suggests the potential scientific merit and the capacity of Marker’s APOLLO study to address an unmet medical need."

Dr. Vera continued: "While our results of the APOLLO study are preliminary, as we move through the dose escalation part of the study, we are encouraged by the objective responses observed in all three study participants treated at City of Hope (Press Release, April 8, 2024) and the lack of cytokine release syndrome (CRS) or immune effector cell associated neurotoxicity syndrome (ICANS) observed. We will continue to closely monitor all patients for long-term treatment effects and durability of response, and with the non-dilutive funding support from NIH we look forward to treating additional participants in this Phase 1 study."

"This grant award is a testimony of our continued commitment to apply for non-dilutive funding and allows us to leverage our data to drive innovation and growth while maximizing shareholder value. Obtaining non-dilutive funding is an ongoing effort, and we are actively applying for additional opportunities as they become available," concluded Dr. Vera.

About the NIH SBIR Program

The NIH Small Business Innovation Research (SBIR) Program sets aside more than $1.2 billion from its Research & Development Funding to specifically support early-stage small businesses throughout the United States. Many companies leverage the NIH SBIR funding to attract the partners and investors needed to take an innovation to market. The Small Business program focuses on a variety of high-impact technologies including research tools, diagnostics, digital health, drugs, and medical devices, and can provide the seed funding needed to bring scientific innovations from bench to bedside.

About MT-601

The Company’s lead product, MT-601, is a multi-tumor associated antigen (multiTAA)-specific T cell product that utilizes a non-genetically modified approach that specifically targets six different tumor antigens upregulated in lymphoma cells (Survivin, PRAME, WT-1, NY-ESO-1, SSX-2, MAGE-A4). Marker is currently investigating MT-601 in the Company-sponsored Phase 1 APOLLO trial (clinicaltrials.gov identifier: NCT05798897) for the treatment of lymphoma patients who are relapsed after or where CD19 CAR-T cell therapy is not an option.

About APOLLO

The APOLLO trial (clinicaltrials.gov Identifier: NCT05798897) is a Phase 1, multicenter, open-label study designed to evaluate the safety and efficacy of MT-601 in participants with lymphoma who relapsed after anti-CD19 CAR-T cell therapy or where anti-CD19 CAR-T cell therapy is not an option. The primary objective of this exploratory Phase 1 clinical trial is to evaluate the safety and preliminary efficacy of MT-601 in participants with various lymphoma subtypes. Under the APOLLO trial, it is anticipated that nine clinical sites across the United States will cumulatively enroll up to approximately 30 participants during the dose escalation phase.

About multiTAA-specific T cells

The multi-tumor associated antigen (multiTAA)-specific T cell platform is a novel, non-genetically modified cell therapy approach that selectively expands tumor-specific T cells from a patient’s/donor’s blood capable of recognizing a broad range of tumor antigens. Unlike other T cell therapies, multiTAA-specific T cells allow the recognition of hundreds of different epitopes within up to six tumor-specific antigens, thereby reducing the possibility of tumor escape. Since multiTAA-specific T cells are not genetically engineered, Marker believes that its product candidates will be easier and less expensive to manufacture, with an improved safety profile, compared to current engineered T cell approaches, and may provide patients with meaningful clinical benefits.

On August 12, 2024 Halda Therapeutics, a biotechnology company developing a novel class of cancer therapies called RIPTACTM (Regulated Induced Proximity TArgeting Chimeras) therapeutics, reported that it has raised new financing of $126 million in a Series B extension, including funding from new investors Deep Track Capital, Frazier Life Sciences, RA Capital Management, Vida Ventures, Boxer Capital and Taiho Ventures, as well as existing investors Canaan Partners, Access Biotechnology, Elm Street Ventures, and Connecticut Innovations (Press release, Halda Therapeutics, AUG 12, 2024, View Source [SID1234645756]). Including this financing, Halda has raised $202 million to date from investors.

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!

Proceeds from the financing will be used to advance two RIPTAC candidates into clinical trials for patients with prostate cancer and breast cancer, initially in the metastatic setting where drug resistance to standard of care is prevalent. Halda’s lead RIPTAC therapeutic, HLD-0915, is expected to initiate a Phase 1 clinical trial in the first half of 2025 for the treatment of patients with metastatic, castration-resistant prostate cancer (mCRPC). The financing will also support the clinical development of a second RIPTAC therapeutic for metastatic breast cancer. In addition, the funding will enable the company to further build its team and to develop additional products using its RIPTAC platform to address other indications with unmet need.

"We are excited to have the support of this leading group of new healthcare investors who share our vision to be a cancer drug innovator. This financing will enable us to bring to patients our oral, selective, and widely applicable cancer cell-killing mechanism that is designed to overcome drug resistance, which is a major shortcoming of many current standard of care cancer treatments," said Kat Kayser-Bricker, PhD, Chief Scientific Officer of Halda Therapeutics. "Our team of talented scientists has made tremendous progress, from inventing the RIPTAC modality to translating our platform into two promising programs in prostate cancer and breast cancer, with our first drug candidate entering the clinic in the first half of 2025 for mCRPC patients."

The RIPTAC modality, now advancing into clinical trials with this financing, has been designed by Halda as a heterobifunctional molecule that targets two proteins for a novel cancer cell-killing mechanism to address a specific cancer type. RIPTAC therapeutics work by a novel "hold and kill" mechanism, bringing together two proteins – a cancer-specific protein and a protein with essential function – resulting in abrogation of the essential cell function, and subsequently, death of the cancer cells while sparing non-cancer tissue where the cancer-specific protein is absent or minimally expressed.

"Novel mechanisms are desperately needed to address resistance to standard of care therapies across a number of tumor types. RIPTAC therapies offer an ability to selectively kill cancer cells based on differential protein expression in orally bioavailable medicines. This innovation has the potential to treat both advanced cancer patients with heterogeneous resistance adaptations, as well as patients with earlier stages of disease. We look forward to working with Halda scientists and clinicians to deliver novel therapies to improve outcomes for cancer patients," said Joe Cabral, Principal at Frazier Life Sciences.

"The team at Halda is creating a new era for oncology treatment with a groundbreaking modality, RIPTAC therapeutics, including medicines that have the potential to deliver solutions for cancer patients beginning with two of the most prevalent cancer types, prostate cancer and breast cancer. In particular, Halda’s lead RIPTAC candidate, HLD‑0915, offers the potential for a mutation-agnostic small molecule approach in the mCRPC setting to address unmet needs for these prostate cancer patients globally," said Arjun Goyal, MD, Co‑Founder and Managing Director, Vida Ventures.

In conjunction with this financing, Rebecca Luse, Principal at Deep Track Capital, Joe Cabral, Principal at Frazier Life Sciences, Nandita Shangari, PhD, Managing Director at RA Capital Management and Arjun Goyal, MD, Co-Founder and Managing Director at Vida Ventures, will join the Halda Board of Directors.

On August 12, 2024 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported financial results and operational updates for the quarter ended June 30, 2024 (Press release, ORIC Pharmaceuticals, AUG 12, 2024, View Source [SID1234645734]).

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 have made strong progress on advancing the pipeline, deepening strategic relationships, and growing the leadership team to add new functional capabilities," said Jacob M. Chacko, M.D., president and chief executive officer. "We are making good progress on the expansion cohorts for ORIC-114 in three different selected patient populations in NSCLC and have initiated combination dosing for ORIC-944 in prostate cancer. The clinical trial collaboration and supply agreements with Bayer and Johnson & Johnson are pivotal steps in supporting those combination cohorts. Finally, we bolstered our leadership team to add commercial and medical affairs capabilities in advance of the potential initiation of multiple registrational trials in 2025. We look forward to sharing further clinical updates in 2025."

Second Quarter 2024 and Other Recent Highlights

ORIC-114: a brain penetrant, orally bioavailable, irreversible EGFR/HER2 inhibitor

Announced the completion of the dose escalation portion of the Phase 1b trial of ORIC-114 and the selection of two provisional recommended phase 2 doses.
Announced first patients dosed across three expansion cohorts in the Phase 1b trial of ORIC-114 in patients with mutated non-small cell lung cancer (NSCLC), including EGFR exon 20 insertion (EGFR exon 20 inhibitor naïve), HER2 exon 20 insertion, and EGFR atypical mutations.
Initiated an extension cohort to evaluate ORIC-114 for the treatment of patients with first-line, treatment-naïve EGFR exon 20 insertion NSCLC.
Expect to report updated Phase 1b data in the first half of 2025.
ORIC-944: a potent and selective allosteric inhibitor of PRC2

Initiated dosing of ORIC-944 in combination with NUBEQA (darolutamide) and in combination with ERLEADA (apalutamide) in the ongoing Phase 1b trial for prostate cancer in first half of 2024.
Entered into clinical trial collaboration and supply agreements with Bayer and Johnson & Johnson to support the ongoing Phase 1b trial of ORIC-944 in combinations with AR inhibitors for the treatment of prostate cancer.
Presented preclinical data at the 2024 AACR (Free AACR Whitepaper) Annual Meeting demonstrating superior drug properties and synergy data in prostate cancer models, reinforcing the promise of ORIC-944 as a potential best-in-class treatment for combination with AR inhibitors.
Discovery Pipeline:

Presented at the 2024 AACR (Free AACR Whitepaper) annual meeting the first preclinical data on ORIC-613, a potential first- and best-in-class development candidate selectively inhibiting PLK4.
Corporate Highlights:

Expanded the leadership team with the appointment of industry veteran Keith Lui as Senior Vice President of Commercial and Medical Affairs.
Second Quarter 2024 Financial Results

Cash, Cash Equivalents and Investments: Cash, cash equivalents and investments totaled $308.5 million as of June 30, 2024, which the company expects will be sufficient to fund its operating plan into late 2026.
R&D Expenses: Research and development (R&D) expenses were $28.9 million for the three months ended June 30, 2024, compared to $18.8 million for the three months ended June 30, 2023, an increase of $10.2 million. For the six months ended June 30, 2024, R&D expenses were $50.9 million, compared to $38.3 million for the six months ended June 30, 2023, an increase of $12.6 million. The increases were due to a net increase in external expenses related to the advancement of product candidates and discovery programs, as well as higher personnel costs, including additional non-cash stock-based compensation of $0.6 million and $1.2 million for the three and six months ended June 30, 2024, respectively.
G&A Expenses: General and administrative (G&A) expenses were $7.1 million for the three months ended June 30, 2024, compared to $6.2 million for the three months ended June 30, 2023, an increase of $0.9 million. For the six months ended June 30, 2024, G&A expenses were $14.1 million, compared to $12.4 million for the six months ended June 30, 2023, an increase of $1.7 million. The increases were primarily due to higher personnel costs, including additional non-cash stock-based compensation of $0.6 million and $1.3 million for the three and six months ended June 30, 2024, respectively.