On August 19, 2024 Daiichi Sankyo (TSE: 4568) reported that the European Medicines Agency (EMA) has validated the Type II Variation application for ENHERTU (trastuzumab deruxtecan) as a monotherapy for the treatment of adult patients with unresectable or metastatic HER2 low (defined as IHC 1+ or IHC 2+/ISH-) or HER2 ultralow (defined as IHC 0 with membrane staining) breast cancer who have received at least one endocrine therapy in the metastatic setting (Press release, AstraZeneca, AUG 19, 2024, View Source [SID1234645999]).

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ENHERTU is a specifically engineered HER2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN).

Validation confirms that the application is complete and commences the scientific review process by the EMA’s Committee for Medicinal Products for Human Use. This application is based on data from the DESTINY-Breast06 phase 3 trial presented as a late-breaking oral session at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) (#ASCO24) Annual Meeting.

"This submission builds on our existing indication for ENHERTU in patients with HER2 low metastatic breast cancer and an expanded approval would enable the potential for use in an earlier disease setting as well as in a broader patient population that now includes HER2 ultralow," said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. "We look forward to working closely with the EMA to potentially bring this medicine to more patients in the EU."

Additional regulatory submissions for ENHERTU in this indication are underway globally.

About DESTINY-Breast06

DESTINY-Breast06 is a global, randomized, open-label, phase 3 trial evaluating the efficacy and safety of ENHERTU (5.4 mg/kg) versus investigator’s choice of chemotherapy (capecitabine, paclitaxel or nab paclitaxel) in patients with HR positive, HER2 low (defined as IHC 1+ or IHC 2+/ISH-) or HER2 ultralow (defined as IHC 0 with membrane staining) advanced or metastatic breast cancer. Patients in the trial had no prior chemotherapy for advanced or metastatic disease and received at least two lines of prior endocrine therapy in the metastatic setting. Patients also were eligible if they had received one prior line of endocrine therapy combined with a CDK4/6 inhibitor in the metastatic setting and experienced disease progression within six months of starting first-line treatment or received endocrine therapy as an adjuvant treatment and experienced disease recurrence within 24 months.

The primary endpoint is progression-free survival (PFS) in the HR positive, HER2 low patient population as measured by blinded independent central review (BICR). Key secondary endpoints include PFS by BICR in the overall trial population (HER2 low and HER2 ultralow), overall survival (OS) in patients in the HER2 low patient population and OS in the overall trial population. Other secondary endpoints include objective response rate, duration of response, time to first subsequent treatment or death, time to second subsequent treatment or death and safety. Analysis of the HER2 ultralow subgroup was not powered to demonstrate statistical significance.

DESTINY-Breast06 enrolled 866 patients (n=713 for HER2 low and n=153 for HER2 ultralow) at multiple sites in Asia, Europe, North America, Oceania and South America. For more information about the trial, visit ClinicalTrials.gov.

About Breast Cancer and HER2 Expression

Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide.1 More than two million breast cancer cases were diagnosed in 2022 with more than 665,000 deaths globally.1 In Europe, approximately 557,000 cases of breast cancer are diagnosed annually.2 While survival rates are high for those diagnosed with early breast cancer, only about 30% of patients diagnosed with or who progress to metastatic disease are expected to live five years following diagnosis.3

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors, including breast cancer.4 Patients with high levels of HER2 expression (IHC 3+ or IHC2+/ISH+) are classified as HER2 positive and treated with HER2 targeted therapies, representing approximately 15 to 20% percent of all breast cancers.5 Historically, tumors that were not classified as HER2 positive were classified as HER2 negative, despite the fact that many of these tumors still carry some level of HER2 expression.6 It is estimated that approximately 60% to 65% of HR positive, HER2 negative breast cancers are HER2 low and potentially an additional 25% may be HER2 ultralow.7,8

Endocrine therapies are widely given consecutively in the early lines of treatment for HR positive metastatic breast cancer.9 However, following two lines of endocrine therapy, further efficacy with additional endocrine treatment is often limited.9 The current standard of care following endocrine therapy is chemotherapy, which is associated with poor response rates and outcomes.9,10,11,12

Prior to the approval of ENHERTU following chemotherapy in HER2 low metastatic breast cancer based on the DESTINY-Breast04 trial, there were no targeted therapies approved specifically for patients with HER2 low expression.13 There are no targeted therapies specifically approved for patients with HER2 ultralow expression.14

About ENHERTU

ENHERTU (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the U.S. only) is a HER2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, ENHERTU is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC scientific platform. ENHERTU consists of a HER2 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

ENHERTU (5.4 mg/kg) is approved in more than 65 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2 positive (IHC 3+ or in-situ hybridization (ISH)+) breast cancer who have received a prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial.

ENHERTU (5.4 mg/kg) is approved in more than 65 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2 low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.

ENHERTU (5.4 mg/kg) is approved in more than 35 countries worldwide for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations, as detected by a locally or regionally approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 trial. Continued approval in the U.S. for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

ENHERTU (6.4 mg/kg) is approved in more than 45 countries worldwide for the treatment of adult patients with locally advanced or metastatic HER2 positive (IHC 3+ or IHC 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01, DESTINY-Gastric02 and/or DESTINY-Gastric06 trials. Full approval in China for this indication will depend on whether a randomized controlled confirmatory clinical trial can demonstrate clinical benefit in this population.

ENHERTU (5.4 mg/kg) is approved in the U.S. for the treatment of adult patients with unresectable or metastatic HER2 positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options based on efficacy results from the DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02 trials. Continued approval for this indication in the U.S. may be contingent upon verification and description of clinical benefit in a confirmatory trial.

On August 19, 2024 ImmunoPrecise Antibodies Ltd. (the "Company" or "IPA") (NASDAQ: IPA), an AI-driven biotherapeutics company, reported a groundbreaking achievement: the ability to engineer antibodies entirely through computer simulations using LENSai (Press release, ImmunoPrecise Antibodies, AUG 19, 2024, View Source [SID1234645982]). This marks a significant milestone for the biotechnology industry. Additionally, the antibodies produced by IPA are highly specific to a challenging oncology target located within the Tumor Microenvironment (TME).

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This achievement was made possible by the patented LENSai technologies, which began from an exceptionally challenging starting point: the target protein had no previously known structural information. Despite this, the LENSai platform was able to model the protein’s structure and accurately engineer antibodies specifically tailored to bind to it. This is particularly significant because designing effective therapeutics without prior structural knowledge of the target is a major hurdle in drug discovery, often requiring extensive experimentation and resources. LENSai’s ability to overcome this challenge entirely in silico highlights its advanced capabilities in computational biology and its potential to revolutionize the field of antibody engineering.

The potential therapies were engineered to bind exclusively to the oncology target under specific conditions. Importantly, it was demonstrated that these therapies do not bind to similar proteins known to be present on healthy cells and tissues, which is crucial because such binding typically leads to the negative side effects seen in chemotherapy. These findings highlight LENSai’s ability to address one of the toughest challenges in optimizing antibodies for oncology.

"This marks a significant milestone for the biotechnology industry, demonstrating LENSai’s ability to engineer highly specific and validated antibodies for the exceedingly difficult environment around tumors, and doing so entirely on a computer," said Dr. Jennifer Bath, President and CEO of IPA. "This success, elevated by the fact that important details of the protein being targeted were unknown, represents a major feat in the application of LENSai in generating targeted and specific therapies for the potential treatment of cancer. Moreover, our continuous advancements and integrations have significantly enhanced our ability to develop these therapies faster, more efficiently, and at a reduced cost compared to traditional methods."

Historically, biologic drug discovery has been a risky, time-consuming, and expensive endeavor, with failure rates exceeding 90%. Recent data indicates that it now costs approximately $1.3 billion and takes an average of 10 to 15 years to bring a single new drug to market, with costs potentially rising even higher depending on the complexity of the drug and therapeutic area​. The market has seen major successes like Humira, which has shown potential in the tumor microenvironment and has generated over $20 billion in annual sales. Similarly, Keytruda has demonstrated effectiveness in modulating the tumor microenvironment and has generated over $14 billion annually. However, the time, cost, and risk associated with developing such biologics have historically limited the number of these therapies that can be pursued, creating a bottleneck in the availability of life-saving treatments.

"The successful application of LENSai, along with laboratory validation of these novel antibodies, underscores LENSai’s potential to accelerate the development of precision-targeted treatments, aimed at more effective cancer therapies with fewer side effects," stated Dr. Dirk Van Hyfte, MD, PhD, Co-Founder and Head of Innovation at BioStrand, an IPA subsidiary. "What LENSai has accomplished today is just one of the reasons we firmly believe in its ability to bring potentially life-changing biologics to patients with the power of our AI."

On August 16, 2024 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA) ("Iovance" or the "Company"), a biotechnology company focused on innovating, developing, and delivering novel polyclonal tumor infiltrating lymphocyte ("TIL") therapies for patients with cancer, reported that on August 15, 2024 (the "Date of Grant"), the Company approved the grant of inducement stock options and restricted stock units covering an aggregate of 289,710 shares of Iovance’s common stock to twenty-four new, non-executive employees (Press release, Iovance Biotherapeutics, AUG 16, 2024, View Source [SID1234645960]).

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The awards were granted under Iovance’s 2021 Inducement Plan, which was adopted on September 22, 2021 and amended on January 12, 2022, March 13, 2023, and February 26, 2024 and provides for the granting of equity awards to new employees of Iovance by the Company’s compensation committee in accordance with Nasdaq Listing Rule 5635(c)(4). Each of the stock options granted as referenced in this press release has an exercise price of $10.67, the closing price of Iovance’s common stock on the Date of Grant. Each stock option and restricted stock unit vests over a three-year period, with one-third of the shares vesting on the first anniversary of the employee’s start date (the "First Vesting Date"), and the remaining shares vesting in eight quarterly installments over the next two years, commencing with the first quarter following the First Vesting Date, subject to continued employment with the Company through the applicable vesting dates.

On August 16, 2024 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a Phase 3 clinical stage pharmaceutical company with a broad portfolio of drug candidates targeting hard-to-treat tumors and viruses, reported the pricing of a public offering of an aggregate of 2,466,368 shares of its common stock (or common stock equivalents in lieu thereof), Series A warrants to purchase up to 2,466,368 shares of common stock and Series B warrants to purchase up to 2,466,368 shares of common stock, at a combined public offering price of $2.23 per share (or per common stock equivalent in lieu thereof) and accompanying warrants (Press release, Moleculin, AUG 16, 2024, View Source [SID1234645961]).

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The Series A warrants have an exercise price of $2.23, are exercisable immediately upon Shareholder Approval (as defined below) and will expire upon the earlier of (i) the 2 year anniversary of the date of Stockholder Approval (as defined below) and (ii) the 60th day following the date the Company releases interim data for the first subject group from the MIRACLE trial whereby the complete remission rate for either doses of the Company’s study drug is greater than placebo. The Series B warrants have an exercise price of $2.23, are exercisable immediately upon Shareholder Approval (as defined below) and will expire upon the earlier of (i) the 5 year anniversary of the date of Stockholder Approval (as defined below) and (ii) the 6 month anniversary following the date the Company releases final topline data from the MIRACLE trial and documented a statistically significant improvement in the primary efficacy endpoint. Pursuant to Nasdaq Listing Rule 5635(d), the exercise of the Series A warrants and Series B warrants is subject to shareholder approval (the "Shareholder Approval"). The closing of the offering is expected to occur on or about August 19, 2024, subject to the satisfaction of customary closing conditions.

H.C. Wainwright & Co. is acting as the exclusive placement agent for the offering.

The gross proceeds from the offering, before deducting the placement agent’s fees and other offering expenses payable by the Company, are expected to be approximately $5.5 million and up to an additional approximately $11.0 million in gross proceeds if the warrants are fully exercised for cash. The Company intends to use the net proceeds from this offering to advance Annamycin and its other two drug portfolios through clinical development, advance the remainder of the Company’s existing portfolio through preclinical studies and into INDs or their equivalent, sponsor research at MD Anderson and HPI, and for working capital.

The securities described above are being offered pursuant to a registration statement on Form S-1 (File No. 333-280951), which was declared effective by the Securities and Exchange Commission (the "SEC") on August 15, 2024. The offering is being made only by means of a prospectus forming part of the effective registration statement relating to the offering. A preliminary prospectus relating to the offering has been filed with the SEC. Electronic copies of the final prospectus, when available, may be obtained on the SEC’s website at View Source and may also be obtained by contacting H.C. Wainwright & Co., LLC at 430 Park Avenue, 3rd Floor, New York, NY 10022, by phone at (212) 856-5711 or e-mail at [email protected].

The Company also has agreed to amend certain existing warrants to purchase up to an aggregate of 895,834 shares of common stock that were previously issued in December 2023 and have an exercise price of $9.60 per share such that the amended warrants will have a reduced exercise price of $2.23 per share effective upon the closing of the offering, will be exercisable beginning on the effective date of Stockholder Approval of the issuance of the shares upon exercise of the warrants and will expire five years from the date of Stockholder Approval.

This press release shall not constitute an offer to sell or a solicitation of an offer to buy any of the securities described herein, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.

On August 16, 2024 Personalis, Inc. (Nasdaq: PSNL) and Tempus AI, Inc. (Nasdaq: TEM) reported that the companies have expanded their commercial relationship. The companies agreed in November 2023 to collaborate and bring ultra-sensitive MRD testing to market and launched their efforts at the recent ASCO (Free ASCO Whitepaper) meeting (Press release, Personalis, AUG 16, 2024, View Source [SID1234645962]). Tempus is serving as exclusive commercial partner for Personalis’ ultra-sensitive tumor-informed MRD product for broad patient adoption in breast and lung cancers, and for immunotherapy monitoring across all solid tumors.

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Following positive reaction and exceptionally strong demand, the companies have agreed to accelerate their efforts, expanding under the following key terms:
•
Tempus to accelerate its commercialization efforts over the first two years

•
Personalis to increase the quantity of patient samples it will accept over the corresponding period

•
Tempus to invest approximately $36 million into Personalis

"We are pleased that our early access program is proceeding well and demand is strong," said Chris Hall, CEO of Personalis. "We believe the expansion of the relationship with Tempus will allow us to better capitalize on the opportunity."

Under the agreement, Tempus agreed to exercise its existing warrants to purchase 9.2 million shares of common stock in accordance with their terms at an average purchase price of $2.00 and to purchase an additional 3.5 million shares of common stock at a price per share of $5.07, which was the last reported closing price of Personalis’ common stock as reported on The Nasdaq Global Market on August 15, 2024, for a total investment of approximately $36 million in Personalis. As a result, Tempus will own approximately 19.3 percent of Personalis’ outstanding common stock following the closing of the transactions.