On January 22, 2024 BioNTech SE (Nasdaq: BNTX, "BioNTech") and Duality Biologics (Suzhou) Co., Ltd. ("DualityBio") reported that the first patient with metastatic breast cancer has been treated in a pivotal Phase 3 trial evaluating the efficacy and safety of the next-generation antibody-drug conjugate ("ADC") candidate BNT323/DB-1303 targeting the Human Epidermal Growth Factor Receptor 2 ("HER2"), a cancer cell surface protein (Press release, BioNTech, JAN 22, 2024, View Source [SID1234639405]).

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Breast cancer is the most commonly diagnosed cancer worldwide and the leading cause of death from malignant tumors in women globally.1,2 The breast cancer subtype, which is defined by the expression of hormone receptors ("hormone receptor-positive", "HR+") and a low expression level of the HER2 protein ("HER2-low") on the cancer cell surface, accounts for approximately 40 % to 45 % of patients in advanced, metastatic disease stage.3 HER2 has been shown to be a suitable target structure for the treatment of breast cancers with intermediate and high HER2 expression.4 HER2-directed therapies have been ineffective in the past in patients with tumors with low expression levels of the protein.5 Recent studies have indicated that next-generation ADCs may have the potential to transfer the impact of HER2-directed therapies to HER2-low tumors.6

The global, multi-center, open-label, randomized Phase 3 trial (NCT06018337) will assess the efficacy and safety of BNT323/DB-1303 compared to standard-of-care single-agent chemotherapy in chemotherapy-naïve patients with HR+ and HER2-low metastatic breast cancer that have progressed on hormone therapy. The trial is expected to enroll 532 patients at more than 223 clinical sites worldwide, initially in China, followed by sites in the United States, Europe, and additional regions. The study’s primary endpoint is progression-free survival. Secondary endpoints include overall survival, objective response rate, duration of response, and safety.

"For patients with advanced HR+/HER2-low breast cancers who progressed after primary therapy, single-agent palliative chemotherapy is the most common regimen to control the disease and reduce mortality. BNT323/DB-1303 has been designed with the aim to combine the selectivity of antibodies with the cancer cell-killing properties of chemotherapy, thereby aiming to minimize the toxicity of the chemotherapeutic agents for patients," said Prof. Özlem Türeci, M.D., Chief Medical Officer and Co-Founder at BioNTech. "Our objective is to further expand the impact of HER2-targeted ADC therapies to chemotherapy naïve patients in metastatic disease stage who express HER2 at low levels at earliest possible treatment lines, seeking to extend the therapeutic window and improve outcomes for these patients."

"The initiation of the Phase 3 trial marks an important step in the development of our next-generation ADC candidate with the first indication progressing into pivotal evaluation," said Vivian Gu, M.D., Chief Medical Officer at DualityBio. "Results from our Phase 1/2 clinical study indicate a robust mechanism of action of BNT323/DB-1303 and have demonstrated preliminary efficacy and a manageable safety profile. We look forward to further advancing this differentiated ADC candidate."

The Phase 3 trial is based on positive safety and efficacy data from a Phase 1/2 study (NCT05150691) with BNT323/DB-1303 in patients with advanced/metastatic solid tumors. Data presented at ASCO (Free ASCO Whitepaper) 2023 demonstrated encouraging anti-tumor activity in heavily pretreated patients with HER2-low breast cancer with an objective response rate of 38.5% and a disease control rate of 84.6%. BNT323/DB-1303 was well tolerated with a manageable safety profile across all evaluated patients with advanced/metastatic solid tumors.

The milestone is in furtherance of BioNTech and DualityBio’s strategic objective to advance the product candidate into late-stage development in multiple high unmet medical need cancer indications. The Phase 3 trial initiation marks a major landmark in BioNTech’s and DualityBio’s strategic collaboration initiated in April 2023. The collaboration aims to accelerate the development of differentiated antibody-drug conjugate therapeutics for solid tumors. BioNTech will hold commercial rights globally (excluding Mainland China, Hong Kong Special Administrative Region, and Macau Special Administrative Region), while DualityBio will retain commercial rights for Mainland China, Hong Kong Special Administrative Region, and Macau Special Administrative Region.

Further information for media: Fact Sheet about BNT323/DB-1303

About BNT323/DB-1303
BNT323/DB-1303 is a third-generation topoisomerase-1 inhibitor-based ADC targeting HER2 which was built from DualityBio’s proprietary Duality Immune Toxin Antibody Conjugates ("DITAC") platform. HER2 is a surface-expressed protein on solid tumors and has been linked to the aggressive growth and spread of cancer cells, making it a potential target for innovative cancer therapeutics. The candidate has exhibited antitumor activity in both HER2-positive and HER2-low tumor models as well as in several solid tumor indications, including patients with breast, gastric, endometrial, biliary tract cancers, and other advanced solid tumors. Preclinical data and preliminary clinical data for BNT323/DB-1303 indicate its potential to target HER2 receptors on solid tumors irrespective of expression level with a manageable safety profile and a potentially expanded therapeutic window. BNT323/DB-1303 is currently being evaluated in an ongoing Phase 1/2 study (NCT05150691) in patients with advanced/metastatic solid tumors and in a pivotal Phase 3 study (NCT06018337) in patients with Hormone Receptor-positive ("HR+") and Human Epidermal Growth Factor Receptor 2 ("HER2")-low, metastatic breast cancer that have progressed on hormone and/or cyclin-dependent kinase 4/6 ("CDK4/6") therapy. The BNT323/DB-1303 program received the Fast Track designation and Breakthrough Therapy designation from the U.S. Food and Drug Administration ("FDA") for the treatment of endometrial cancer in 2023.

On January 22, 2024 AIM ImmunoTech Inc. (NYSE American: AIM) ("AIM" or the "Company") reported that the first subject has been enrolled at Erasmus Medical Center ("Erasmus MC") in a Phase 1b/2 clinical trial combining AIM’s Ampligen (rintatolimod) with AstraZeneca’s anti-PD-L1 immune checkpoint inhibitor Imfinzi (durvalumab) for the treatment of late-stage pancreatic cancer (the "DURIPANC Study") (Press release, AIM ImmunoTech, JAN 22, 2024, View Source [SID1234639404]).

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Data strongly suggests Ampligen has therapeutic synergy when combined with checkpoint inhibitors – potentially increasing cancer treatment efficacy and subject survival rates. A successful DURIPANC Study could make AIM an especially attractive partnership or buyout target for Big Pharma. Data already strongly suggests that Ampligen synergistically enhances anti-PD-1 therapy. Strong positive clinical data from the DURIPANC study would also support our belief that Ampligen could synergistically enhance anti-PD-L1 therapies. Such broad-spectrum success could create value. AIM recently took an important step to secure potential stockholder value when it received a U.S. patent for the use of Ampligen as part of a combination therapy with an anti-PD-L1 antibody, which is an immune checkpoint inhibitor that helps the body attack tumor cells.

The DURIPANC Study is an investigator-initiated, exploratory, open-label, single-center study with the full name "Combining anti-PD-L1 immune checkpoint inhibitor durvalumab with TLR-3 agonist rintatolimod in patients with metastatic pancreatic ductal adenocarcinoma for therapy effect." The primary objective of the Phase 1b portion is to determine the safety of combination therapy with Imfinzi and Ampligen. The primary objective of the Phase 2 portion is to determine the clinical benefit rate of the combination therapy.

"We expect to complete the Phase 1b portion of the study within six months," states Prof. Casper H.J. van Eijck, MD, PhD, the DURIPANC Study’s Coordinating Investigator.

See ClinicalTrials.gov: NCT05927142 for more information.

AIM CEO Thomas K. Equels stated: "Ampligen’s potential as part of a combination therapy is a relatively simple equation. One, elevated PD-L1 expression – which is known to occur in pancreatic cancer – has been associated with increased exhaustion of peripheral and intra-tumoral cytotoxic T cells, commonly called ‘killer’ T cells. Two, data indicate that Ampligen has the potential to mitigate T cell exhaustion. Three, Ampligen can increase the number and activity of immune cells in the blood and tumor. And four, Imfinzi inhibits PD-L1 activity, thereby making those activated immune cells in the tumor microenvironment more effective at fighting the cancerous tumor. Data from our Dutch Early Access Program strongly supports Ampligen’s potential to increase progression-free survival and overall survival. Our hope for the DURIPANC trial is that at a minimum we see an even longer period of stable disease, also called progression-free survival. However, we also believe this combination of drugs has the potential to decrease tumor size or even to cure the cancer, which is defined as being tumor free for at least five years. That would be a dramatic breakthrough in the treatment of a highly lethal and treatment-resistant human cancer."

The study is expected to enroll up to 18 subjects in its Phase 1b portion and up to 25 subjects in its Phase 2 portion. Subjects will start with Ampligen 200 mg via IV infusion twice per week for a total of 6 weeks (12 doses). Ampligen dose will be escalated to 400 mg according to a 3+3 DLT design. The first dose of Ampligen will be administered preferably 4-6 weeks after the last chemotherapy FOLFIRINOX dose. After two doses of Ampligen, the first dose of durvalumab 1500 mg via IV infusion will be introduced in week 2. Patients will continue to receive 1500 mg durvalumab via IV infusion every 4 weeks for up to a maximum of 48 weeks (up to 12 doses/cycles) with the last administration on week 48 or until confirmed disease progression according to Response Evaluation Criteria in solid Tumors (RECIST 1.1), unless there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met.

On January 20, 2024 Radiopharm Theranostics Limited (ASX:RAD) (Radiopharm or the Company), a developer of diagnostic and therapeutic radiopharmaceutical products, reported it has entered into strategic agreements with Lantheus Holdings, Inc. (LNTH.NASDAQ), a leading radiopharmaceutical-focused company, and its affiliates (Lantheus). Lantheus has agreed to make an initial equity investment of A$7.5 million (US$4.99 million) and will have an option to invest a further A$7.5 million (US$5 million) within 6 months on the same terms. Additionally, Radiopharm has agreed to transfer two of its early preclinical assets to Lantheus for A$3.0 million (US$2.0 million) pursuant to a separate transfer and development agreement.

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The net proceeds of Lantheus’ investment will be used by the Company for drug manufacturing, clinical trials and general working capital.

Subject to shareholder approval for the purposes of ASX Listing Rule 7.1, under a subscription agreement entered into with Radiopharm (Subscription Agreement), Lantheus has subscribed for up to:

a) A$7.5 million (US$4.99 million) at A$0.05 (US$0.033) per share;
b) unlisted options with a six-month term after the date the subscription shares are issued to invest up to an additional A$7.5 million (US$5 million) at A$0.05 (US$0.033) per share; and
c) one option for every four shares subscribed for (inclusive of any shares further subscribed for in the next six months), exercisable at A$0.06 per option expiring in August 2026.

Under a separate transfer and development agreement, Radiopharm has assigned and sub-licensed two of its preclinical assets to Lantheus for A$3.0 million (US$2.0 million). Assets covered under the agreement are a TROP2 targeting nanobody and a LRRC15 targeting mAb.

B. Riley Securities is acting as financial advisor to the Company on the Lantheus transactions.

Further terms of Lantheus investment

Under the Subscription Agreement, and subject to shareholder approval at an upcoming extraordinary general meeting, Lantheus will be issued up to:

149,625,180 shares under the Placement amounting to a subscription amount of US$4.99 million (A$7.5 million) (Lantheus Shares), subject to 12 months escrow;
149,925,040 unlisted options with an exercise price of A$0.05 (5 cents) and an expiry date six months from the date of issue of the Lantheus Shares (Lantheus Options), with 12 months escrow applying to any shares issued on exercise of the options; and
37,406,295 options (i.e. one (1) new option for every four (4) new Lantheus Shares issued) with an exercise price of A$0.06 and an expiry date approximately 2 years from the date the Lantheus Shares are issued (Lantheus Placement Options),
subject to and upon exercise of the Lantheus Options, up to 37,481,260 additional options (on the basis of one (1) new option for every four (4) new Lantheus Shares issued upon exercise of the Lantheus Options) with an exercise price of A$0.06 and an expiry date approximately 2 years from the date the Lantheus Shares are issued (Second Tranche Lantheus Options),
(together, the Lantheus Interests).

Other key terms of the Subscription Agreement (noting undefined terms have the meanings ascribed to them in the Subscription Agreement) include:

Other key terms of the Lantheus Options, Lantheus Placement Options and Second Tranche Lantheus Options are:
Subject to compliance with the Australian Corporations Act, the options may be exercised during the exercise period and, within five Business Days of exercise, the Company will:
allot and issue the number of Shares as specified in the Exercise Notice and for which the Exercise Price has been received by the Company in cleared funds; and
apply for official quotation on the ASX of Shares issued pursuant to the exercise of the Subscription Option; and
Shares issued as a result of the exercise of an option will be fully paid and rank pari passu in all respects with all other Shares then on issue.
The Company provides standard warranties regarding its standing and the issue of the Lantheus Interests and the Company indemnifies Lantheus against any loss to Lantheus’ investment in the Company which Lantheus suffers or is liable for arising directly or indirectly from a warranty being untrue or inaccurate. Lantheus provides standard warranties regarding its standing.
Lantheus may terminate the agreement before completion if:
the Company is prevented from issuing or allotting the Lantheus Shares by the order of a court of competent jurisdiction or by a government agency;
The Australian Securities and Investment Commission or the Takeovers Panel commences, or threatens to commence, any inquiry, hearing investigation or regulatory action or issues any order or interim order or other proceedings in relation to the Company, the Lantheus Shares or the Lantheus Options;
the Company commits a material breach of the Subscription Agreement; or
any of the Company warranties cease to be true and accurate.
Lantheus may terminate the Subscription Agreement if Shareholder approval (in the form contemplated above) is not obtained within a three-month period.
As is customary with these types of arrangements, the agreement contains typical investor protections such as negative covenants and representations and warranties by the Company.
Other key terms of the transfer and development agreement include:

The Company and its subsidiary, Radiopharm Theranostics (USA), Inc., a Nevada corporation, together have agreed to transfer and assign to Lantheus each of their title, and interest in the TROP2 targeting nanobody and a LRRC15 targeting mAb assets, including all data and information regarding the compounds and technologies; and
As is customary with these types of arrangements, the agreement contains typical assignee protections such as risk allocation clauses and representations and warranties made by the Company and Radiopharm Theranostics (USA), Inc. in respect of each entity’s standing and its ownership of and rights in the assets being assigned and sold.

(Press release, Radiopharm Theranostics, JAN 20, 2024, View Source [SID1234661591])

On January 20, 2024 Bristol Myers Squibb (NYSE: BMY) reported results from the Phase 3 CheckMate -8HW trial evaluating Opdivo (nivolumab) plus Yervoy (ipilimumab) compared to investigator’s choice of chemotherapy (mFOLFOX-6 or FOLFIRI with or without bevacizumab or cetuximab) as a first-line treatment for patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (mCRC) (Press release, Bristol-Myers Squibb, JAN 20, 2024, View Source;8HW-Trial/default.aspx [SID1234639399]). The dual immunotherapy combination of Opdivo and Yervoy demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of progression-free survival (PFS) as assessed by Blinded Independent Central Review (BICR), with a reduction in the risk of disease progression or death by 79% (Hazard Ratio [HR]: 0.21; 95% Confidence Interval [CI]: 0.14-0.32; p<0.0001) compared to chemotherapy in patients with centrally confirmed MSI-H/dMMR mCRC.

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These late-breaking data (Abstract #LBA768) will be featured in an oral presentation at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium on Saturday, January 20 at 9:15 a.m. Pacific Time and will be highlighted as part of the Congress’ official press program.

Improvement in PFS was noted beginning at approximately three months and was sustained throughout. Median PFS was not yet reached in the Opdivo plus Yervoy arm (95% CI: 38.4-NE) vs. 5.9 months in the chemotherapy arm (95% CI: 4.4-7.8). Consistent PFS benefit was observed across all pre-specified subgroups, including patients with KRAS or NRAS mutations, and those with baseline liver, lung, or peritoneal metastases.

The safety profile for the combination of Opdivo plus Yervoy remained consistent with previously reported data and was manageable with established protocols, with no new safety signals identified. Grade 3/4 treatment-related adverse events (TRAEs) occurred in 23% of patients in the Opdivo plus Yervoy arm and 48% of patients in the chemotherapy arm. Any grade TRAE-related discontinuation was 17% in the Opdivo plus Yervoy arm and 32% in the chemotherapy arm.

"Patients with MSI-H/dMMR metastatic colorectal cancer are less likely to benefit from chemotherapy," said Thierry Andre, M.D., Head of the Medical Oncology Department, Sorbonne University and Hospital Saint-Antoine, Paris, France. "An impressive improvement in PFS and sustained benefit beginning at three months was observed with nivolumab plus ipilimumab versus chemotherapy in this trial. These results demonstrate the meaningful efficacy of this combination with practice-changing potential for this patient population."

Opdivo plus Yervoy is the first dual immunotherapy regimen to demonstrate significant efficacy benefit compared to chemotherapy as first line treatment in MSI-H/dMMR mCRC.

"With research from the full CheckMate clinical development program, BMS has revolutionized the oncology landscape and helped change survival expectations for people with cancer. Today, with these data from CheckMate -8HW, we showed that Opdivo plus Yervoy reduced the risk of disease progression or death by an unprecedented 79%," said Dana Walker, M.D., M.S.C.E., vice president, global program lead, gastrointestinal and genitourinary cancers, Bristol Myers Squibb. "These results build on the benefit of Opdivo and Yervoy in MSI-H/dMMR metastatic colorectal cancer as previously demonstrated in CheckMate -142 and reinforce our commitment to exploring the potential of these therapies to help more patients in need."

CheckMate -8HW is ongoing to assess the second dual primary endpoint of PFS in patients receiving Opdivo plus Yervoy compared to Opdivo alone across all lines of therapy, as well as secondary endpoints, including overall survival (OS).

Bristol Myers Squibb thanks the patients and investigators involved in the CheckMate -8HW clinical trial.

About CheckMate -8HW

CheckMate -8HW (NCT04008030) is a Phase 3 randomized, open-label trial evaluating Opdivo plus Yervoy compared to Opdivo alone or investigator’s choice chemotherapy (mFOLFOX-6 or FOLFIRI with or without bevacizumab or cetuximab) in patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (mCRC).

Approximately 830 patients were randomized to receive either Opdivo monotherapy (Opdivo 240 mg Q2W for six doses, followed by Opdivo 480 mg Q4W), Opdivo plus Yervoy (Opdivo 240 mg plus Yervoy 1 mg/kg Q3W for four doses, followed by Opdivo 480 mg Q4W), or investigator’s choice of chemotherapy. The dual primary endpoints of the trial are progression-free survival (PFS) per blinded independent central review (BICR) for Opdivo plus Yervoy compared to investigator’s choice of chemotherapy in the first line setting and PFS per BICR for Opdivo plus Yervoy compared to Opdivo alone across all lines of therapy. The trial also includes several secondary safety and efficacy endpoints, including overall survival (OS).

The study is ongoing to assess the second dual primary endpoint of PFS in patients receiving Opdivo plus Yervoy compared to Opdivo alone across all lines of therapy, as well as secondary endpoints.

About MSI-H or dMMR Colorectal Cancer

Colorectal cancer (CRC) is a cancer that develops in the colon or the rectum, which are part of the body’s digestive or gastrointestinal system. CRC is the third most commonly diagnosed cancer in the world. In 2020, it is estimated that there were approximately 1,931,000 new cases of the disease; it is the second leading cause of cancer-related deaths among men and women combined.

Mismatch repair deficiency (dMMR) occurs when the proteins that repair mismatch errors in DNA replication are missing or non-functional, leading to microsatellite instability-high (MSI-H) tumors. Approximately 5-7% of metastatic CRC patients have dMMR or MSI-H tumors; they are less likely to benefit from conventional chemotherapy and typically have a poor prognosis.

On January 19, 2024 Adaptam Therapeutics reported ERC Proof of Concept projects funded by the European Research Council (ERC) are designed for researchers who currently hold ERC projects and wish to explore the commercial potential of their research (Press release, Adaptam Therapeutics, JAN 19, 2024, View Source [SID1234657090]). These projects are focused on establishing proof of concept for an idea generated during ERC-funded projects. The €150,000 grant is primarily aimed at activities directed to exploring the commercial or societal potential of the research.

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Specifically, the "TAM-ADaCT" project presented by Adaptam Therapeutics and now supported by the ERC Proof of Concept program aims to study the efficacy of novel antibody-drug conjugates (ADCs) directed against suppressor cells in the tumor microenvironment. This recently awarded ERC Proof of Concept grant builds upon a previous ERC Starting grant secured by Prof. Asis Palazon while at CIC bioGUNE.

Various immunotherapy strategies have shown promise in clinical trials, especially the use of inhibitors targeting so-called immune "checkpoint" receptors. However, current immunotherapies are effective in only a small fraction of patients, presenting a medical need that must be addressed across multiple cancer types. Notably, the tumor microenvironment has specific characteristics that affect the immune response, including reduced oxygenation, aberrant vascularization, and altered nutrient availability. All these factors influence the success of immunotherapies.

Prof. Palazon commented: "We are thrilled to receive this ERC Proof of Concept grant, which represents a pivotal step in advancing our innovative approach to targeting tumor-associated macrophages. By focusing on the immunosuppressive myeloid environment within tumors, we aim to develop a novel antibody-drug conjugate that could significantly enhance the efficacy of cancer treatments. Our goal is to offer more effective therapeutic options for patients who currently do not benefit from existing immunotherapies."