On August 13, 2024 Bolt Biotherapeutics (Nasdaq: BOLT), a clinical-stage biopharmaceutical company developing novel immunotherapies for the treatment of cancer, reported financial results for the second quarter ended June 30, 2024, and provided a business update (Press release, Bolt Biotherapeutics, AUG 13, 2024, View Source [SID1234645792]).

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!

"During the second quarter, we continued to make significant progress across our two programs, BDC-3042 and BDC-4182, following our strategic pipeline prioritization in May," said Willie Quinn, Chief Executive Officer. "For our lead program BDC-3042, we completed the safety evaluation period for cohort 5 with no dose-limiting toxicities. BDC-3042 continues to be well tolerated to date, and we are now enrolling patients into cohort 6. We will be presenting a poster on BDC-4182, our claudin 18.2-targeting BoltbodyTM ISAC, at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 39th Annual Meeting, and we look forward to sharing more data on this program in November. I’m proud that the team has not missed a beat working through our strategic pipeline prioritization and restructuring. Our strong cash position allows us to move these programs through early clinical development and provides us with cash runway through mid-2026."

Recent Highlights and Anticipated Milestones
•Advanced to cohort 6 in the Phase 1 study of BDC-3042 in patients with advanced cancers. BDC-3042 is a proprietary agonist antibody that targets Dectin-2, an immune-activating receptor expressed by tumor-associated macrophages (TAMs). This single-agent, dose-escalation Phase 1 clinical study is evaluating BDC-3042 in patients with metastatic or unresectable triple-negative breast cancer (TNBC), colorectal cancer, clear cell renal cell carcinoma, head and neck cancer, non-small cell lung cancer (NSCLC), ovarian cancer, or melanoma.
•Preparing BDC-4182 to start clinical trials in 2025. BDC-4182 is a next-generation BoltbodyTM ISAC clinical candidate targeting claudin 18.2, a novel, clinically validated target in oncology with expression in gastric/gastroesophageal junction cancer, pancreatic cancer, and other tumor types. BDC-4182 has advanced into IND-enabling activities, supported by in vitro and in vivo experiments demonstrating potent anti-tumor activity in multiple preclinical models. A poster on BDC-4182 will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 39th Annual Meeting, which will take place from November 6-10, 2024, in Houston, Texas.

•Collaborations with Genmab and Toray continue to progress. The Company continues to work with its collaborators to discover and develop ISACs for the treatment of cancer. Recent developments with Genmab supported the extension of the original initial research phase of the collaboration.
•Cash, cash equivalents, and marketable securities were $97.5 million as of June 30, 2024. Cash on hand is expected to fund multiple milestones and operations through mid-2026.

Second Quarter 2024 Financial Results

•Collaboration Revenue – Collaboration revenue was $1.3 million for the quarter ended June 30, 2024, compared to $1.4 million for the same quarter in 2023. Revenue in the comparative periods was generated from services performed under R&D collaborations as we fulfill our performance obligations.

•Research and Development (R&D) Expenses – R&D expenses were $15.4 million for the quarter ended June 30, 2024, compared to $15.6 million for the same quarter in 2023.

•General and Administrative (G&A) Expenses – G&A expenses were $4.9 million for the quarter ended June 30, 2024, compared to $5.6 million for the same quarter in 2023. The decrease between the comparable periods was mainly due to a decrease in salary and related expenses primarily due to a decrease in bonus expense as a result of the restructuring plan.

•Restructuring Charges – Restructuring charges were $3.6 million for the quarter ended June 30, 2024, consisting of $2.9 million of one-time termination benefits such as severance costs and related benefits and $0.7 million of non-cash stock-based compensation expense as a result of the restructuring plan. There were no restructuring charges in the quarter ended June 30, 2023.

•Loss from Operations – Loss from operations was $22.6 million for the quarter ended June 30, 2024, compared to $19.8 million for the same quarter in 2023.

About the Boltbody Immune-Stimulating Antibody Conjugate (ISAC) Platform
Bolt Biotherapeutics’ Boltbody ISAC platform harnesses the precision of antibodies with the power of the innate and adaptive immune system to generate a productive anti-cancer response. Each Boltbody ISAC candidate comprises a tumor-targeting antibody, a non-cleavable linker, and a proprietary immune stimulant. The antibody is designed to target one or more markers on the surface of a tumor cell and the immune stimulant is designed to recruit and activate myeloid cells. Activated myeloid cells initiate a positive feedback loop by releasing cytokines and chemokines, chemical signals that attract other immune cells and lower the activation threshold for an immune response. This increases the population of activated immune system cells in the tumor microenvironment and promotes a robust immune response with the goal of generating durable therapeutic responses for patients with cancer.

On August 12, 2024 Biogen Inc. (the "Company") reported to have entered into a credit agreement with Bank of America, N.A., as Administrative Agent, Swing Line Lender and the L/C Issuer, and the lenders party thereto (the "Credit Agreement") (Filing, 8-K, Biogen, AUG 12, 2024, View Source [SID1234645889]). The Credit Agreement provides for a $1.5 billion five-year unsecured, revolving credit facility (the "Revolving Credit Facility"). The Revolving Credit Facility includes borrowing capacity in the form of letters of credit of up to $25.0 million and $20.0 million in swing line loans.

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!

Borrowings under the Revolving Credit Facility are available for general corporate purposes. No proceeds from the Revolving Credit Facility were drawn down as of the closing date of the Credit Agreement.

Revolving loans under the Credit Agreement (other than swing line loans) will bear interest at rate per annum equal to (i) Term SOFR, with respect to revolving loans denominated in dollars, (ii) EURIBOR, with respect to revolving loans denominated in euros, (iii) TIBOR, with respect to revolving loans denominated in yen, (iv) SONIA, with respect to revolving loans denominated in sterling, and (v) SARON, with respect to revolving loans denominated in Swiss francs, in each case, subject to a floor of 0.00% per annum, plus an applicable margin ranging from 0.625% to 1.375% depending on the ratings of the Company’s non-credit enhanced, senior unsecured long-term debt, as determined by either Standard & Poor’s or Moody’s (the "Debt Ratings") or, at the Company’s option, with respect to revolving loans denominated in dollars, a Base Rate equal to the higher of (i) the Bank of America prime rate, (ii) the Federal Funds Rate plus 0.50% and (iii) Term SOFR plus 1.00%, subject to a floor of 0.00% per annum (the "Base Rate"), plus an applicable margin ranging from 0.000% to 0.375% based on the Company’s Debt Ratings. Swing line loans will bear interest at the Base Rate plus the applicable margin for Base Rate loans.

In addition to paying interest on any outstanding principal under the Revolving Credit Facility, the Company will pay (i) a commitment fee in respect of the unutilized commitments thereunder and (ii) customary letter of credit fees and agency fees. The commitment fees range from 0.050% to 0.150% per annum based on the Company’s Debt Ratings.

The Revolving Credit Facility will terminate and all amounts outstanding thereunder are due and payable five years after the closing date, subject to certain extension options as set forth in the Credit Agreement. Under the Revolving Credit Facility, voluntary prepayments are permitted, in whole or in part, without premium or penalty, other than customary breakage costs. The Revolving Credit Facility requires quarterly interest payments or, in the case of borrowings that bear interest by reference to a term rate, at the end of the interest period therefor, with the principal due on the maturity date.

The Credit Agreement contains customary representations and warranties, affirmative and negative covenants and events of default. The Credit Agreement also includes a financial covenant requiring the Company to maintain, measured as of the end of each fiscal quarter, a maximum consolidated leverage ratio of 3.75 to 1.0 (which may be temporarily increased to 4.25 to 1.0 upon the election of the Company as a result of a material acquisition, subject to customary limitations).

A copy of the Credit Agreement is attached hereto as Exhibit 10.1 and is incorporated herein by reference. The description of the Credit Agreement is a summary only and is qualified in its entirety by the terms of the Credit Agreement.

On August 12, 2024 Summit Therapeutics Inc. (NASDAQ: SMMT) ("Summit," "we," or the "Company") reported that the primary analysis of the Phase III HARMONi-2 trial featuring its novel, potential first-in-class investigational bispecific antibody, ivonescimab, will be presented as part of the Presidential Symposium at the International Association for the Study of Lung Cancer’s (IASLC) 2024 World Conference on Lung Cancer (WCLC 2024) in San Diego, California (Press release, Summit Therapeutics, AUG 12, 2024, View Source [SID1234645757]). The presentation will take place on Sunday, September 8, 2024 at 8:37 am PT (11:37 am ET).

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!

HARMONi-2 evaluated monotherapy ivonescimab against monotherapy pembrolizumab in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose tumors have positive PD-L1 expression (PD-L1 TPS >1%). HARMONi-2 is a single region, multi-center, double-blinded Phase III study conducted in China sponsored by our collaboration partner, Akeso, Inc. (Akeso, HKEX Code: 9926.HK), with data generated and analyzed by Akeso.

There are no known Phase III clinical trials in NSCLC that have shown a statistically significant efficacy improvement compared to pembrolizumab in a head-to-head setting.

On May 30, 2024, Akeso announced that in HARMONi-2 ivonescimab monotherapy achieved a statistically significant improvement in the trial’s primary endpoint, progression-free survival (PFS), when compared to monotherapy pembrolizumab. The PFS benefit was demonstrated across clinical subgroups, including those with PD-L1 low expression (PD-L1 TPS 1-49%), PD-L1 high expression (PD-L1 TPS ≥50%), squamous and non-squamous histologies, as well as other high-risk patients.

The trial results will be presented by Dr. Caicun Zhou, Chief Physician and Director of the Department of Medical Oncology at Shanghai Pulmonary Hospital, Tongji University School of Medicine, and President-Elect of IASLC.

A second presentation titled, "A Phase II Study of Perioperative Ivonescimab Alone or Combined with Chemotherapy in Resectable Non-Small Cell Lung Cancer" will include data from the Phase II trial, AK112-205, which is conducted and sponsored by Akeso, featuring data from ivonescimab in the perioperative, early-stage NSCLC setting.

About the WCLC 2024 Presentations

First Presentation

Presentation Title: Phase 3 Study of Ivonescimab (AK112) vs. Pembrolizumab as First-line Treatment for PD-L1-positive Advanced NSCLC: Primary Analysis of HARMONi-2

Presenter: Caicun Zhou, MD, PhD

WCLC Presentation No.: PL02.04

Session Date & Time: Sunday, September 8, 8:37 am PT (11:37 am ET)

Second Presentation

Presentation Title: A Phase II Study of Perioperative Ivonescimab Alone or Combined with Chemotherapy in Resectable Non-Small Cell Lung Cancer

Presenter: Xiaoliang Zhao, MD

WCLC Presentation No.: OA01.06

Session Date & Time: Sunday, September 8, 11:17 am PT (2:17 pm ET)

About Ivonescimab

Ivonescimab, known as SMT112 in Summit’s license territories, the United States, Canada, Europe, Japan, Latin America, including Mexico and all countries in Central America, South America, and the Caribbean, the Middle East, and Africa, and as AK112 in China and Australia, is a novel, potential first-in-class investigational bispecific antibody combining the effects of immunotherapy via a blockade of PD-1 with the anti-angiogenesis effects associated with blocking VEGF into a single molecule. Ivonescimab displays unique cooperative binding to each of its intended targets with multifold higher affinity when in the presence of both PD-1 and VEGF.

This could differentiate ivonescimab as there is potentially higher expression (presence) of both PD-1 and VEGF in tumor tissue and the tumor microenvironment (TME) as compared to normal tissue in the body. Ivonescimab’s tetravalent structure (four binding sites) enables higher avidity (accumulated strength of multiple binding interactions) in the tumor microenvironment with over 18-fold increased binding affinity to PD-1 in the presence of VEGF in vitro, and over 4-times increased binding affinity to VEGF in the presence of PD-1 in vitro (Zhong, et al, SITC (Free SITC Whitepaper), 2023). This tetravalent structure, the intentional novel design of the molecule, and bringing these two targets into a single bispecific antibody with cooperative binding qualities have the potential to direct ivonescimab to the tumor tissue versus healthy tissue. The intent of this design, together with a half-life of 6 to 7 days (Zhong, et. al., SITC (Free SITC Whitepaper), 2023), is to improve upon previously established efficacy thresholds, as well as to improve upon side effects and safety profiles associated with these targets.

Ivonescimab was engineered by Akeso Inc. (HKEX Code: 9926.HK) and is currently engaged in multiple Phase III clinical trials. Over 1,800 patients have been treated with ivonescimab in clinical studies globally.

Summit has begun its clinical development of ivonescimab in non-small cell lung cancer (NSCLC), commencing enrollment in 2023 in two multi-regional Phase III clinical trials, HARMONi and HARMONi-3.

HARMONi is a Phase III clinical trial which intends to evaluate ivonescimab combined with chemotherapy compared to placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who have progressed after treatment with a 3rd generation EGFR TKI (e.g., osimertinib).

HARMONi-3 is a Phase III clinical trial which is designed to evaluate ivonescimab combined with chemotherapy compared to pembrolizumab combined with chemotherapy in patients with first-line metastatic squamous NSCLC.

In addition, Akeso has recently had positive read-outs in two single-region (China), randomized Phase III clinical trials for ivonescimab in NSCLC, HARMONi-A and HARMONi-2.

HARMONi-A was a Phase III clinical trial which evaluated ivonescimab combined with chemotherapy compared to placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who have progressed after treatment with an EGFR TKI.

HARMONi-2 is a Phase III clinical trial evaluating monotherapy ivonescimab against monotherapy pembrolizumab in patients with locally advanced or metastatic NSCLC whose tumors have positive PD-L1 expression (PD-L1 TPS >1%).

Ivonescimab is an investigational therapy that is not approved by any regulatory authority in Summit’s license territories, including the United States and Europe. Ivonescimab was approved for marketing authorization in China in May 2024.

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 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.