On July 21, 2021 AnchorDx, a world-leading developer of cancer screening and early detection solutions, on July 13, 2021, reported that it was awarded a Breakthrough Device Designation ("BTD")[1] by the US Food and Drug Administration (FDA) for UriFind (or "the Test"), an early detection test for bladder cancer based on urine DNA methylation detection (Press release, AnchorDx, JUL 21, 2021, View Source [SID1234585041]). This is the first BTD granted to liquid biopsy test for bladder cancer detection in China.

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Compared with the traditional gold standard cystoscopy for bladder cancer detection, UriFind is non-invasive, painless and easy to operate allowing for the accurate detection of bladder cancer by simply collecting random urine, providing the Test and conducting methylation detection of exfoliated cell DNA in urine. The performance of the Test has shown to be as strong as that of cystoscopy, and significantly better than exfoliative cytology and Fluorescence in situ hybridization (FISH) in the detection of early and non-muscle invasive bladder cancer (NMIBC). The Test demonstrates increased advantages in the detection of early, micro, residual and recurrent bladder cancer, and provides a sound basis for the clinical diagnosis of bladder cancer.

The Test’s research achievements have been published in The Journal of Clinical Investigation[2] and Clinical Epigenetics. Following years’ of real-world sample accumulation and verification by AnchorDx, the accuracy, sensitivity and specificity of UriFind have now reached 89.3%, 87.4% and 91.5% respectively. During the FDA-BTD approval process, AnchorDx provided head-to-head experiment results with another internationally approved product, proving the Test’s superior performance in detection sensitivity and ease-of-use.

UriFind’s detection method has been included into the newly released 2021 Guidelines for Diagnosis and Treatment of Bladder Cancer in China and has also gained EU CE marking. In addition, AnchorDx has also passed the medical device quality management system certification – TUV ISO 13485 Certification.

At present, AnchorDx’s UriFind has entered the registered clinical trials stage in China, and clinical trials in the United States will be launched soon. Once the Test obtains the US market authorization from FDA, a four-year national medicare coverage[3] will be provided. As an innovative biotechnology enterprise in China with a global perspective, AnchorDx constantly promotes the registration and certification of advanced cancer early detection technology around the world and is making every effort to accelerate the global market authorization of UriFind, with a view to enabling it to serve more population in need as soon as possible.

On July 21, 2021 Bayer reported that An investigational breast cancer drug Bayer recently licensed from Systems Oncology has shown strong antitumor responses in mice, offering early clues as to why the German pharma shelled out $25 million for the preclinical asset last September (Press release, Bayer, JUL 21, 2021, View Source [SID1234585129]).

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The drug, dubbed ErSO, works by over-activating a normally tumor-protective pathway to make it toxic for cancer cells. It eradicated both primary and metastatic tumors in mouse models of estrogen receptor-positive breast cancers, according to results published in Science Translational Medicine.

The pathway ErSO targets is called the anticipatory Unfolded Protein Response (aUPR). Through mild and transient activation, aUPR prepares ER-positive cancer cells for growth and protects them from stress such as anticancer treatment.

But in a PNAS study in 2015, a research team from the University of Illinois at Urbana-Champaign led by biochemistry professor David Shapiro, Ph.D., showed that massive and sustained activation of aUPR with a drug could instead inhibit protein synthesis, depriving ER-positive breast cancer cells key building blocks necessary for survival.

For the new research, Shapiro and colleagues identified ErSO as a more potent aUPR hyper-activator that could selectively kill ER-positive breast cancer cells.

RELATED: ASCO (Free ASCO Whitepaper): Sanofi says early amcenestrant data could see it be ‘endocrine backbone therapy’ in breast cancer

In multiple mouse models of ER-positive breast cancer, ErSO quickly killed off tumor cells in high numbers just days after treatment. Combined data from four mouse models showed that 38 of 39 tumors regressed by over 95%, with about half of cases reduced to undetectable levels, the team reported. Even tumors that didn’t completely disappear and regrew after stopping treatment still remained fully sensitive to another cycle of ErSO, the team found.

In another mouse model bearing mutant, patient-derived breast tumors with low expression of ER, oral ErSO treatment outperformed standard-of-care therapies tamoxifen and AstraZeneca’s Faslodex (fulvestrant) at blocking tumor growth, the team found.

"Many of these breast cancers shrink by more than 99% in just three days," Shapiro said in a statement. "ErSO is fast-acting and its effects on breast cancers in mice are large and dramatic."

What’s more, the Bayer drug also significantly reduced cancer metastases at multiple locations, including the lung, bone and brain, the researchers showed.

RELATED: AstraZeneca drops breast, prostate cancer programs in Q4 pipeline cull

The success of Faslodex has prompted several biopharma companies to develop next-generation selective ER downregulators (SERDs). They include Sanofi, which is moving its drug, amcenestrant, into a phase 3 trial against tamoxifen after showing promising early results in combination with Pfizer’s CDK4/6 inhibitor Ibrance.

Roche is pairing its SERD drug, giredestrant, with Ibrance in the phase 3 persevERA trial. And Radius Health is working with Menarini on an oral SERD dubbed elacestrant. It expects phase 3 data from the EMERALD trial later this year.

The UIUC team noted that in mouse models, second-generation SERDs typically induced moderate regression of primary tumors. Those that were tested against metastases showed limited efficacy. And resistance is still a risk with CDK4/6 inhibitors.

Compared with the common inhibitory modes of action against ER, ErSO could offer "a turn-on approach to convert a tumor-selective protective pathway into a lethal, targeted anticancer response," the researchers wrote in the study. The drug’s ability to target metastatic tumors and its activity in ER-low tumors that are traditionally considered ER-negative could broaden its potential therapeutic range, the researchers said.

Bayer picked up global rights to ErSO in September for $25 million upfront, and Systems Oncology is eligible to receive milestone payments of up to $345 million.

While the current study found the drug was well tolerated in mice and dogs, further safety analyses are needed before it can be tested in humans, the UIUC team said. The researchers also plan to explore ErSO’s use against other types of ER-positive cancers.

On July 21, 2021 AmerisourceBergen (NYSE: ABC), Cardinal Health (NYSE: CAH) and McKesson (NYSE: MCK) reported that they have negotiated a comprehensive proposed settlement agreement which, if all conditions are satisfied, would result in the settlement of a substantial majority of opioid lawsuits filed by state and local governmental entities (Press release, Cardinal Health, JUL 21, 2021, View Source [SID1234585008]).

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While the companies strongly dispute the allegations made in these lawsuits, they believe the proposed settlement agreement and settlement process it establishes, which is outlined below, are important steps toward achieving broad resolution of governmental opioid claims and delivering meaningful relief to communities across the United States. The companies remain deeply concerned about the impact the opioid epidemic is having on individuals, families, and communities across the nation and are committed to being part of the solution.

The proposed settlement agreement is the result of years of negotiation with state attorneys general and representatives of the subdivisions. If the proposed settlement agreement and settlement process leads to final settlement through the process outlined below, it would collectively provide thousands of communities across the United States up to approximately $21 billion over 18 years. It would also establish a clearinghouse that consolidates data from all three distributors, which will be available to the settling states to use as part of their anti-diversion efforts.

Subject to certain future milestones described below and the level of participation, the companies would be responsible for up to the following contributions, payable over 18 years:

AmerisourceBergen: $6.4 billion
Cardinal Health: $6.4 billion
McKesson: $7.9 billion
The proposed settlement agreement would become binding only if all conditions outlined below are satisfied:

Approval of State and
Territorial Participation

For the next 30 days, all U.S. States, territories and Washington DC will have the opportunity to join the settlement, except West Virginia which settled previously with the companies. After the conclusion of the state sign-on period, each company will independently determine whether a sufficient number of states have joined to warrant continuing with the political subdivision sign-on period.

Approval of Political
Subdivision Participation

If the distributors decide that sufficient states have joined, each participating state will continue to offer its political subdivisions, including those that have not sued, the opportunity to participate in the settlement for an additional 120-day period. After the conclusion of the political subdivision sign-on period, each company will independently determine whether a sufficient number of states and a sufficient number of political subdivisions have joined for the settlement to proceed to implementation.

If the conditions are satisfied, the settlement would become effective 60 days after the distributors determine that there is sufficient participation to proceed. During this 60-day period, the participating states and the distributors would cooperate to obtain consent judgments in each participating state embodying the terms of the settlement. The companies will make their first annual settlement payment into escrow on or before September 30, 2021, and the payment will be disbursed following the effective date, or returned to distributors if the settlement does not become effective.

If, however, a settlement cannot be finalized and plaintiffs instead choose to pursue their claims in court, the companies will continue to assert their strong legal defenses in pending litigation.

This settlement process only addresses the claims of U.S. state attorneys general and political subdivisions in participating states. The West Virginia subdivisions and Native American tribes are not part of this settlement process.

On July 21, 2021 Turnstone Biologics Corp., a clinical-stage biotechnology company pioneering the development of cancer immunotherapies, reported the successful completion of an $80 million Series D financing co-led by PFM Health Sciences and Point72 (Press release, Turnstone Biologics, JUL 21, 2021, View Source [SID1234585024]). Additional new investors Eventide Asset Management, Surveyor Capital (a Citadel company), Ridgeback Capital Investments, Takeda Ventures Inc., CaaS Capital, JM Family Enterprises, Inc., Northleaf Capital Partners, 404 Bio and an undisclosed investor were joined by existing investors Versant Ventures, OrbiMed, F-Prime Capital, Sectoral Asset Management, Sixty Degree Capital, Brace Pharma Capital and Teralys Capital.

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"Turnstone is developing next-generation medicines in two of the most clinically validated fields of immunotherapy for solid tumors," said Sammy Farah, Ph.D., MBA, President and CEO at Turnstone. "This oversubscribed financing will allow us to advance our vision to benefit millions of cancer patients underserved by current treatment options. We are delighted to welcome PFM Health Sciences, Point72 and additional new investors to Turnstone, and we are grateful for the steadfast support of our existing syndicate."

Proceeds from the financing will be used to advance Turnstone’s pipeline of programs from its oncolytic virus and TIL therapy platforms. Turnstone’s lead oncolytic virus candidate, RIVAL-01/TAK-605, is currently in the dose escalation stage of a Phase 1/2a clinical study in solid tumors conducted in collaboration with Takeda Pharmaceutical Company Limited ("Takeda"). The product is derived from the Company’s proprietary vaccinia virus platform that has been engineered for enhanced immune-stimulation and tumor cell selectivity, large transgene carrying capacity for local expression of encoded therapeutics, and with flexibility for both intratumoral and intravenous delivery.

Turnstone’s lead TIL therapy candidate, TIDAL-01, is expected to enter clinical development by early next year. The program builds on clinically validated treatment protocols while enriching for the most relevant T-cells for tumor eradication, preserving broad antigen diversity, and minimizing time to treatment for patients, with the ultimate goal of extending the benefit of TIL therapy across a wider range of solid tumor types.

Concurrent with the financing, Santhosh Palani, Ph.D., CFA, Partner at PFM Health Sciences, will join the Company’s Board of Directors. "The addition of the TIL therapy platform to Turnstone’s existing viral immunotherapy creates a significant strategic advantage for the Company," said Dr. Palani. "Turnstone’s TIL programs represent the most direct approach to advance the field as there is strong clinical evidence that selection of tumor reactive T-cells can drive better patient outcomes. The enhanced benefit and curative potential that Turnstone can uniquely bring by combining viral immunotherapy with TILs to solve challenges associated with solid tumors, drives yet another layer of excitement."

On July 21, 2021 Ascentage Pharma (6855.HK), a globally focused biotechnology company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported that the US Food and Drug Administration (FDA) recently granted an Orphan Drug Designation (ODD) to the company’s MDM2-p53 inhibitor, APG-115 (alrizomadlin), for the treatment of stage IIB-IV melanoma (Press release, Ascentage Pharma, JUL 21, 2021, View Source [SID1234585042]). This marks the fifth ODD granted to alrizomadlin, after those for the treatment of gastric cancer, acute myeloid leukemia, soft tissue sarcoma, and retinoblastoma. To date, Ascentage Pharma has obtained a total of twelve ODDs from the FDA, continuing to set the record for the number of ODDs granted to any Chinese biopharmaceutical company.

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The term "orphan drugs" refers to pharmaceutical products developed for the prevention, diagnosis, and treatment of rare diseases or conditions. In the United States, an orphan indication is defined as a disease or condition with a prevalence of less than 200,000 patients in the country. Since the Orphan Drug Act was passed in 1983, the US government has provided incentives and policy support to encourage development of orphan drugs. This ODD by the FDA qualifies alrizomadlin for a range of development incentives, including a tax credit on expenditures incurred in clinical studies, a waiver of the New Drug Application (NDA) fee, possible research grant awarded by the FDA, and most importantly, 7 years of US market exclusivity upon approval.

Melanoma is a potentially deadly dermatologic malignancy that has been increasingly prevalent globally. The current lifetime risk of developing melanoma is 1 in 63 in the US1. In 2019, an estimated 96,480 patients have been diagnosed with melanoma and about 7230 patients with melanoma have died in the United States2. The prognosis of patients with of melanoma is closely associated with the stage of the disease at diagnosis. A US Surveillance, Epidemiology, and End Results (SEER) database review of melanoma cases from 2011 to 2015 identified approximately 75% of patients were diagnosed at stage I, 15% at stage II, 7.5% at stage III, and 2.5% at stage IV3.

Since 2011, remarkable progress has been achieved in the clinical treatment of patients with metastatic or unresectable melanoma. Targeted therapies such as mitogen-activated protein (MAP) kinase inhibitors and immunotherapies have dramatically improved patients’ overall survival and quality of life4-6. Immunotherapies, namely immune checkpoint inhibitors (ICIs) such as anti-CTLA-4, anti-PD-1, and anti-PD-L1 monoclonal antibodies have been extensively studied and broadly used in clinical treatment. However, significant number of patients will eventually develop resistance to ICIs, and there is no approved treatment yet for patients with ICI-resistant melanoma.

Being developed by Ascentage Pharma, alrizomadlin is an orally administered, selective, small-molecule MDM2-p53 inhibitor. Preclinical studies showed that alrizomadlin combined with PD-1 blockade enhances antitumor activities by triggering adaptive antitumor immunity. At the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, Ascentage Pharma reported updated results from a Phase II study of alrizomadlin in combination with pembrolizumab that demonstrated promising antitumor activity and safety. The PD-1/PD-L1 inhibitor-resistant melanoma cohort which was treated with alrizomadlin plus pembrolizumab reported 1 patient with complete response, an objective response rate (ORR) of 24.1%, and a disease control rate of 55.2%. These results signified the synergy between alrizomadlin and immune-oncologic drugs, and a potential regimen that could bring hope to patients with ICI-resistant melanoma.

"At present, there is a large unmet medical need for the treatment of melanoma. Therefore, this ODD for alrizomadlin bears tremendous significance," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "As the fifth ODD granted to alrizomadlin, and the twelfth obtained by Ascentage Pharma, this designation reaffirms Ascentage Pharma’s leadership in the number of ODDs granted to any Chinese biopharmaceutical company, demonstrating our capabilities in global innovation. Moving forward, we will continue to pursue our mission of addressing unmet medical needs in China and around the world. The FDA’s supporting policy for orphan drug development will help us to further accelerate the clinical development of alrizomadlin and other drug candidates in our pipeline and hopefully we can bring these potential novel therapies to patients as soon as possible."