Corcept Initiates DAZALS – A Phase 2 Trial in Amyotrophic Lateral Sclerosis

 Corcept Therapeutics Incorporated (NASDAQ: CORT), a commercial-stage company engaged in the discovery and development of medications to treat severe endocrine, oncologic, metabolic and neurological disorders by modulating the effects of the hormone cortisol, today announced that it has initiated DAZALS – a Phase 2 trial of its proprietary selective cortisol modulator dazucorilant in patients with amyotrophic lateral sclerosis (ALS).

“ALS, also known as Lou Gehrig's disease, is a devastating neuromuscular illness with an urgent need for better treatment," said Bill Guyer, PharmD, Corcept’s Chief Development Officer. "We are excited to initiate this important study in collaboration with TRICALS, the leading ALS academic consortium in Europe."

"Dazucorilant showed great promise in animal models of ALS – improving motor performance and reducing neuroinflammation and muscular atrophy," said principal investigator Dr. Leonard van den Berg, chairman of TRICALS and professor of neurology at the University Medical Center Utrecht in the Netherlands. "I am excited to partner with Corcept to study dazucorilant's potential to significantly improve treatment outcomes for people living with ALS."

DAZALS is a 198-patient, randomized, double-blind, placebo-controlled Phase 2 trial of dazucorilant in patients with ALS. The primary endpoints will be ALS Functional Rating Scale-Revised (ALSFRS-R) total score and safety. Key secondary endpoints include overall survival and quality of life. Additional information about DAZALS can be found here.

https://finance.yahoo.com/news/corcept-therapeutics-initiates-dazals-phase-200500276.html

Amarin Board of Directors Issues Statement in Response to Sarissa

 Amarin Corporation plc (NASDAQ:AMRN) today issued the following statement in response to Sarissa Capital Management LP (“Sarissa”) on behalf of the Amarin Board of Directors:

As a Board, we are unified and supportive of Amarin’s new strategic direction, and the actions management has taken to position the Company for growth and value creation. The Board believes there is tremendous runway for growth as Amarin’s strategic focus shifts toward expanding the business in Europe and other international markets, and recent actions to stabilize our U.S. business materialize. Amarin continues to progress on its comprehensive cost reduction program and other cash preservation initiatives.

Over the past year, our Board, with the assistance of a renowned global search firm, has been executing a deliberate plan to refresh its composition and add directors with skills we believe are necessary to help guide the Company on its new strategic direction. In 2022 alone, this process resulted in the appointment of three independent directors. Our new directors add extensive global biotech, international pharmaceutical experience, as well as specific healthcare investment experience and expertise. We have also made significant changes to our Board leadership, including appointing a new Board Chair, naming new Chairs of the Audit and Remuneration Committees, and the retirement of two long-tenured directors.

The Amarin Board of Directors is committed to best-in-class corporate governance. To this end, identifying and recommending new members for Amarin’s Board is a process we take seriously. Consistent with our ongoing Board refreshment process and our good-faith engagement with Sarissa, the Board has a defined and tailored list of skillsets that we believe are necessary to help guide the Company forward, and we rigorously evaluate any potential candidates’ commitment and contributions they might bring to the Board and the Company. With this in mind, we have interviewed several highly qualified candidates and the Board is in final stages to appoint new independent directors. Throughout the Board’s consideration of these candidates, including Sarissa’s proposed nominees, we have kept Sarissa apprised of the Board’s refreshment process. This process remains ongoing.

https://finance.yahoo.com/news/amarin-board-directors-issues-statement-201500111.html

Illumina to Collaborate with AstraZeneca to Accelerate Drug Target Discovery

  Illumina, Inc.  (NASDAQ: ILMN), a global leader in DNA sequencing and array-based technologies, today announced a strategic research collaboration with AstraZeneca Pharmaceuticals LP, a global, science-led biopharmaceutical company, to accelerate drug target discovery by combining their strengths in artificial intelligence (AI) based genome interpretation and genomic analysis techniques along with industry expertise. The collaboration will evaluate whether a combined framework of these technologies can increase the yield and confidence of target discovery to find promising drugs based on human omics insights.

"Illumina and AstraZeneca are uniquely positioned to improve the efficiency of pharma pipelines by leveraging industry-leading abilities to identify genetic variants that contribute to human disease," said Joydeep Goswami, chief strategy and corporate development officer, interim chief financial officer at Illumina. "By identifying genes that show evidence of human disease causality, the combined framework has the potential to prioritize drug candidates with increased likelihood of approval."

The collaboration leverages Illumina's next generation of AI-based interpretation tools, PrimateAI and SpliceAI, in combination with AstraZeneca's analysis framework for rare variant genomic discoveries—alongside the latter's own AI tools, including JARVIS and in silico predictors like missense tolerance ratio. As part of the research collaboration a framework combining the two companies' AI-based tools will be adopted by AstraZeneca's Centre for Genomics Research to analyze large-scale multi-omics data sets in its digital biobank. The complementary AI tools work to more confidently pinpoint genetic variants that contribute to human diseases, a critical step in the process of developing effective and safe therapies. 

https://www.biospace.com/article/releases/illumina-launches-strategic-research-collaboration-with-astrazeneca-to-accelerate-drug-target-discovery/

Nimbus in Agreement with Lilly for Small Molecule Activators of AMPK

 Nimbus eligible to receive up to $496 million, inclusive of research funding and potential milestone payments, in addition to royalties on net sales

AMPK activation is a promising strategy to treat disorders of dysregulated metabolism

 

Nimbus Therapeutics, a clinical-stage company that is working to design and develop breakthrough medicines through its powerful computational drug discovery engine, today announced it has entered into a research collaboration and exclusive, worldwide license agreement with Eli Lilly and Company (Lilly) for the development and commercialization of novel targeted therapies that activate a specific isoform of AMPK for the treatment of metabolic diseases.

Leveraging Nimbus’s computational drug discovery engine and expertise in structure-based drug design, Nimbus is uniquely positioned to develop isoform-selective small molecule activators of AMPK with potential therapeutic application to a broad range of metabolic disorders.

https://www.biospace.com/article/releases/nimbus-therapeutics-announces-research-collaboration-and-license-agreement-with-lilly-for-small-molecule-activators-of-ampk/?keywords=lilly

BridgeBio Starts Phase 1/2 Trial, Gets Fast Trackfor SHP2 inhibitor BBP-398 Combo with Amgen LUMAKRAS

 - BBP-398, an investigational SHP2 inhibitor, is a potentially optimal agent for use in combination therapies given its continuous, once-daily dosing in addition to synergistic activity with other agents to treat cancers driven by KRAS G12C mutations

- The combination of investigational therapy BBP-398 and LUMAKRAS, if successful, has the potential to address the serious unmet need for patients with KRAS G12C-mutated non-small cell lung cancer (NSCLC).

- This combination trial is designed to target NSCLC driven by a KRAS G12C mutation, one of the most common oncogenic mutations in the United States (US) and European Union (EU); 13% of NSCLC tumors have a KRAS G12C mutation with approximately 30,000 people diagnosed in the US each year

- Preclinical findings demonstrated synergistic efficacy for the combination of the two therapies in a KRAS G12C-mutated NSCLC cell line-derived xenograft model

https://www.biospace.com/article/releases/bridgebio-pharma-announces-first-lung-cancer-patient-dosed-in-phase-1-2-trial-and-us-fda-fast-track-designation-for-shp2-inhibitor-bbp-398-in-combination-with-amgen-s-lumakras-sotorasib-/?keywords=bridgebio

PDS: Expanded Interim Data in Phase 2 Trial Targeting Advanced HPV-Positive Cancers

 PDS Biotechnology Corporation (Nasdaq: PDSB), a clinical-stage immunotherapy company developing a growing pipeline of targeted immunotherapies for cancer and infectious disease, today announced expanded interim data in the Phase 2 clinical trial investigating the PDS0101-based triple combination therapy in advanced human papillomavirus (HPV)-positive cancers.   This Phase 2 study is being conducted at the Center for Cancer Research (CCR) at the National Cancer Institute (NCI), one of the Institutes of the National Institutes of Health. The interim efficacy data from 37 HPV16-positive evaluable patients, including 29 patients in the checkpoint inhibitor (CPI) refractory arm, are consistent with the results presented at ASCO 2022 and affirm the selection of CPI refractory patients as the initial patient population for ongoing clinical development of the triple combination.

The NCI-led Phase 2 clinical trial (NCT04287868) is investigating PDS0101 in combination with two investigational immune-modulating agents – M9241, a tumor-targeting IL-12 (immunocytokine), and bintrafusp alfa, a bifunctional checkpoint inhibitor (PD-L1/ TGF-β) – in recurrent or metastatic HPV-positive cancers in patients who have failed prior therapy. The triple combination is being studied in CPI-naïve and -refractory patients with advanced HPV-positive anal, cervical, head and neck, vaginal, and vulvar cancers. Both M9241 and bintrafusp alfa are owned by Merck KGaA, Darmstadt, Germany.

Highlights of the expanded interim data are as follows:

• Survival data: 66% (19/29) of HPV 16-positive CPI refractory patients in the cohort were alive at a median follow up of 16 months.  Historically, this group has a median overall survival of only 3-4 months. ⁱ
• Safety profile: 48% (24/50) of patients experienced Grade 3 treatment-related adverse events (AEs), and 4% (2/50) patients experienced Grade 4 AEs. There were no grade 5 treatment-related AEs

Results for HPV 16-positive checkpoint inhibitor naïve patients also continue to appear to be encouraging: 75% (6/8) of CPI naïve patients were alive at a median of 25 months of follow up. 38% (3/8) of responders had a complete response. 

https://www.biospace.com/article/releases/pds-biotech-announces-expanded-interim-data-in-pds0101-triple-combination-phase-2-trial-targeting-advanced-hpv-positive-cancers/

Ginkgo Scores Another Big Partner in Merck Biocatalyst Deal

 Ginkgo Bioworks partnered with Merck to use engineered enzymes as biocatalysts for Merck's active pharmaceutical ingredient manufacturing programs, the companies announced Tuesday. 

Ginkgo will engineer up to four enzymes for Merck. The company will use its cell engineering and enzyme design expertise. It will also use its abilities in automated high throughput screening, bioinformatics and manufacturing process optimization to identify optimal strains to Merck's specifications.

Ginkgo notes that biocatalysts are more sustainable, effective and cost-effective than some chemical synthesis steps used in industrial chemical synthesis. It does so by reducing synthesis and purification steps.

In this case, Ginkgo plans to use its proprietary fungal strains and technology platforms to identify and manufacture the enzymes. 

"Ginkgo's fungal strains present a major opportunity for improving biocatalysis," stated Behzad Mahdavi, SVP of biopharma manufacturing and life sciences tools. "E. coli is currently the mainstay host for expressing enzymes, but a large number of enzymes will not express properly in E. coli, and those that do express in E. coli may have better homologs that only express in fungal strains."

The "enzyme optimization project with Merck has the potential to help reduce the cost of goods and enable a more robust supply chain for APIs,' he added. 

Under terms of the partnership, Merck will pay Ginkgo an undisclosed upfront research and development fee. Gingko is also eligible for various milestone payments, both R&D and commercial. The commercial milestones could reach $144 million in aggregate.

Ginkgo calls itself "The Organism Company." It uses a variety of engineered microorganisms to manufacture a wide range of products in a broad swath of industries. This includes biopharma, biosecurity, food and agriculture, and industrial chemicals. 

In September, the Biden Administration announced new investments into biotechnology and biomanufacturing. Part of that initiative includes $30 million for expanding biomanufacturing for APIs, antibiotics and basic materials to manufacturing drugs and to respond to pandemics.

The Department of Defense launched the Tri-Service Biotechnology for a Resilient Supply Chain program that includes more than $270 million over five years. The DoD is also investing $1 billion in bioindustrial domestic manufacturing infrastructure over five years, and the U.S. Department of Agriculture will provide $500 million in grants to support independent, innovative and sustainable fertilizer production using advances in biotechnology and biomanufacturing.

More Momentum for Ginkgo 

Gingko has been on a buying spree lately. Earlier this month, it acquired Circularis and Altar. Circularis focuses on circular RNA (circRNA) and has a screening platform to increase cell and gene therapy treatments for rare diseases.

France-based Altar has a proprietary adaptive evolution platform, which Gingko plans to integrate into its "foundry" to serve Ginkgo's customers across multiple industries, including health care. Altar's technology platform can sustainably adapt microorganisms to conditions required by industrial companies for commercial-scale projects.

Anna Marie Wagner, SVP of corporate development at Ginkgo Bioworks, told BioSpace Ginkgo is always looking for new technologies to improve its own capabilities for its clients. 

In late August, Ginkgo acquired certain epidemiological data infrastructure assets from Baktus, a Delaware-based public benefit corporation. Ginkgo now owns proprietary datasets, modeling and analytic tools, as well as a software platform that can track, model and forecast epidemics and related risks and impacts. It plans to integrate several ongoing epidemiological analysis projects and a team of epidemiologists into its biosecurity and public health initiative, Concentric by Ginkgo.

In July, Ginkgo acquired Zymergen. The company indicated plans to integrate Zymergen's core automation and software technologies to scale strain engineering capacity into its foundry, including Zymergen's machine learning and data science tools.

And Ginkgo is no stranger to big company partnerships. In early August, it announced a breakthrough in its collaboration with Synlogic. Synlogic, in partnership with Ginkgo, developed a new drug candidate for the treatment of gout, SYNB2081. It was the second product to come out of the collaboration.

In July, Ginkgo and Bayer entered into a partnership to expand Ginkgo's platform in agricultural biologics. As part of the arrangement, Ginkgo is acquiring Bayer's 175,000-square-foot West Sacramento Biologics Research & Development site, team and internal discovery and lead optimization platform for about $83 million.

Also in July, Ginkgo launched a new cell programming project as part of a broader collaboration with Sumitomo Chemical Co. Sumitomo will utilize Ginkgo's codebase and organisms engineering expertise to sustainably manufacture molecules for a range of products in a variety of industries. 

In June, Ginkgo inked a collaboration pact with Novo Nordisk to develop novel expression hosts for pharma products.

https://www.biospace.com/article/ginkgo-bioworks-partners-with-merck-on-biocatalysts/