On June 30, 2022 Akebia Therapeutics, Inc. (Nasdaq: AKBA), a biopharmaceutical company with the purpose to better the lives of people impacted by kidney disease, reported that it has executed an agreement to terminate the U.S. and ex-U.S. vadadustat Collaboration and License Agreements with Otsuka Pharmaceutical Co., Ltd. (Otsuka) (Press release, Akebia, JUN 30, 2022, View Source [SID1234616419]). As part of the termination, Otsuka has agreed to pay Akebia a settlement fee of $55 million.

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As a result of the termination of the agreements, Akebia is regaining the rights from Otsuka for vadadustat, an investigational oral hypoxia-inducible factor prolyl hydroxylase inhibitor, in the United States, Europe, China, Russia, Canada, Australia, the Middle East, and certain other territories.

"We continue to believe in the potential of vadadustat as an oral treatment for patients with anemia due to chronic kidney disease, and we are pleased to be regaining the full rights to the product in these important markets," said John Butler, Chief Executive Officer of Akebia. "Otsuka has been a strong partner for many years, and we appreciate their desire to have an efficient transfer of the responsibilities back to Akebia. We plan to continue to pursue approval for vadadustat to make it available to patients in these territories, and we are excited about the potential additional value this brings to Akebia, as we continue to work to build the company into the future."

In October 2021, Otsuka submitted an initial marketing authorization application (MAA) to the European Medicines Agency (EMA) for vadadustat for the treatment of anemia associated with chronic kidney disease (CKD) in adults. The review is in progress. Otsuka and Akebia will coordinate to transfer the MAA to Akebia through processes outlined by the EMA. Vadadustat is also under review in the United Kingdom, Switzerland, and Australia through the Access Consortium. Responsibilities for that review will transfer to Akebia as well at a date to be agreed upon.

In the U.S., Akebia received a Complete Response Letter from the U.S. Food & Drug Administration (FDA) for vadadustat. Akebia plans to evaluate and determine potential next steps for vadadustat in the U.S. following the end of review conference with the FDA.

In the U.S., Akebia separately has a distribution agreement in place with Vifor Pharma, providing potential access to up to 60% of U.S. dialysis patients through existing Vifor Pharma relationships. Mitsubishi Tanabe Pharma Corporation owns development and commercialization rights to vadadustat in Japan and certain other Asian counties.

On June 30, 2022 ROME Therapeutics, a biotechnology company harnessing the power of the dark genome for drug development, reported a new publication in The Proceedings of the National Academy of Sciences (PNAS) which describes the first-ever X-ray crystallography structure of an endogenous reverse transcriptase – specifically human endogenous retrovirus-K (HERV-K) reverse transcriptase (RT) (Press release, Rome Therapeutics, JUN 30, 2022, View Source [SID1234616418]). The structure unlocks therapeutic opportunities for RT inhibitors in cancer, autoimmune and neurodegenerative diseases.

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"A significant portion of the human genome is made up of endogenous retroviruses, which are associated with a range of serious diseases, including cancer. In this publication, we describe for the first time the crystal structure of an endogenous reverse transcriptase, one known as HERV-K RT, and show that it has remarkable similarities to HIV RT, a well-known tractable drug target," said Dennis Zaller, Ph.D., Chief Scientific Officer of ROME. "This achievement is a milestone in the dark genome field and sheds light on opportunities for structure-based drug design based on established anti-viral targets present in the human genome. This work is the result of a great collaboration between ROME’s exceptional structural biology team and world-leading crystallographers."

Repetitive elements in the genome, such as HERV-K, are frequently over-expressed in cancer and elicit biological viral mimicry responses that can alter the tumor microenvironment. Anti-viral drugs with activity against endogenous retrovirus-derived repeats can have therapeutic benefit, as illustrated by a recent study from ROME’s scientific co-founders published in Cancer Discovery showing that a nucleoside reverse transcriptase inhibitor designed for HIV-1 (3TC) led to clinical benefit in 9 of 32 patients with late-stage colorectal cancer. These findings demonstrate the potential of molecules designed for activity against repeat-encoded targets, such as eRT, the first therapeutic target announced by ROME in November 2021.

"This study marks a significant step forward in our understanding of endogenous retroviruses and how they could be targeted to treat disease," said Eddy Arnold, Ph.D., Resident Faculty Member at the Center for Advanced Biotechnology and Medicine (CABM), Board of Governors Professor of Chemistry and Chemical Biology at Rutgers University and Scientific Advisory Board member at ROME. "Characterizing the structure of HIV RT was a critical turning point in designing novel medicines to combat that deadly virus. Similarly, deeper insights into human endogenous RT could pave the way toward a new class of therapies for cancer and other serious diseases."

On June 30, 2022 Twist Bioscience Corporation (NASDAQ: TWST), a company enabling customers to succeed through its offering of high-quality synthetic DNA using its silicon platform, and Ildong Pharmaceutical, reported an agreement under which Ildong will license a suite of Twist VHH antibody libraries to use to discover and develop antibodies for applications in immuno-oncology (Press release, Twist Bioscience, JUN 30, 2022, View Source [SID1234616416]).

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"This collaboration with Twist moves us closer to our vision of becoming a fully global healthcare company while also continuing to drive novel therapies in South Korea through the expansion of our pipeline," said Hongseok Ban, Ph.D. of Ildong Pharmaceutical. "Access to a selection of Twist’s VHH libraries will enable us to complete discovery efforts to select antibody candidates for development as novel immuno-oncology therapies."

"We believe our VHH libraries are extremely versatile in their applications developing novel and next generation therapies. Because they are significantly smaller than a traditional human antibody, they can be combined with other technologies, or used on their own for development of effective therapies," said Emily M. Leproust, Ph.D., CEO and co-founder of Twist Bioscience. "This VHH library licensing agreement with Ildong is our first collaboration with a South Korea-based company and broadens our presence in the Asia-Pacific region."

Under the terms of the agreement, Ildong will license a suite of Twist’s VHH libraries for a period of three years and will use the libraries to conduct research and development activities. Twist will receive an upfront payment, annual maintenance fees and additional payments for success-based clinical and regulatory milestones as well as royalties on product sales.

VHH Antibody Libraries

Antibodies contain two variable domains, the heavy and the light chains. A VHH antibody, also known as a single domain antibody, is the antigen binding domain of the heavy chain, with three complementary determining regions (CDRs), or areas where antigens bind to the antibody. Twist’s VHH libraries use novel methods that combine synthetic and natural approaches to maximize diversity in the 10 billion antibody library, creating high quality VHH libraries for use against any protein target. The small size of the VHH antibodies allow them to access targets that traditional antibodies cannot, with tight binding affinity. The modular nature of VHH antibodies supports creation of bi- or multi-specific antibodies ideal for developing next generation therapies specific to oncology, autoimmune disease and virology.

About Ildong Pharmaceutical

Ildong Pharmaceutical
Health Research Center for sharing happier lives

As a leading pharmaceutical company in South Korea, Ildong Pharmaceutical has been dedicated and committed to the development and supply of superior pharmaceutical products that contribute to the health and well-being of people around the world. Ildong Pharmaceutical is steadfast in its vision of continuously growing with its customers as a leading global company by providing solutions for disease prevention and developing new solutions for healthier and happier lives.

Ildong Pharmaceutical has earned the trust of our customers with ethical drugs franchise for chronic disease and cancer therapies, antibiotics, and digestive and circulatory drugs, in addition to well-known OTC brands such as Biovita(probiotics product) and Aronamin(multivitamin). Ildong Pharmaceutical is on the road to reaching its vision of becoming a global total healthcare company with various new drug pipelines including Besivo(hepatitis B therapy), which is the 28th novel drug in South Korea, as well as new innovative drug pipelines and new businesses for health functional foods, medical devices, cosmetics, and beverages.

On June 30, 2022 Avacta Group plc (AIM: AVCT), a clinical stage biopharmaceutical company developing innovative cancer therapies and powerful diagnostics based on its proprietary Affimer and pre|CISION platforms, reported that LG Chem Life Sciences (LG Chem), the life sciences division of the South Korean LG Group, has exercised its renewal option as part of the ongoing collaboration with Avacta, triggering a license renewal fee payment to Avacta of $2 million (Press release, LG Chem, JUN 30, 2022, View Source [SID1234616415]).

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Under the terms of the agreement, LG Chem has the exclusive rights to develop and commercialise, on a global basis, Avacta’s Affimer PD-L1 inhibitor with Affimer XT serum half-life extension for a range of indications. LG Chem has exercised its license renewal option and will progress the PD-L1/XT candidate by commencing pre-clinical studies which are intended to form the basis of an Investigational New Drug (IND) submission.

In December 2018, Avacta and LG Chem entered into a multi-target development agreement to develop Affimer therapeutics in several disease areas. In 2020 the companies agreed to expand this drug development partnership to include Avacta’s Affimer XT technology, which can be used to control the time a drug spends in the blood.

Dr Alastair Smith, Chief Executive Officer of Avacta, commented: "I am very pleased with the progress being made by our partners LG Chem with the Affimer PD-L1 checkpoint inhibitor programme, which includes the Affimer XT serum half-life extension technology. The initiation of IND enabling studies represents a significant step towards first-in-human clinical trials of the Affimer platform, which is a key value driver for the technology and for Avacta."

On June 30, 2022 Cyclacel Pharmaceuticals, Inc. (NASDAQ: CYCC, NASDAQ: CYCCP; "Cyclacel" or the "Company"), a biopharmaceutical company developing innovative medicines based on cancer cell biology, reported that it has achieved key business objectives in the first half of 2022 and provided a review of progress with its two clinical stage drug candidates (Press release, Cyclacel, JUN 30, 2022, View Source [SID1234616414]).

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"We are highly encouraged by clinical safety and anticancer activity observed with oral fadraciclib monotherapy to date," said Spiro Rombotis, President and Chief Executive Officer. "Based on available information we believe that a favorable tolerability profile, daily dosing and target engagement against CDK2 and CDK9 differentiates fadraciclib as potentially best-in-class. Data collected to date in fifteen patients suggest that fadraciclib may have activity across a range of solid tumors and lymphomas. With respect to our second strategic priority, we are actively advancing development of CYC140, our oral PLK1 inhibitor, and enrolling patients in a registration-directed Phase 1/2 study in solid tumors and lymphomas. We look forward to reporting additional data at our R&D Day in the fall of 2022."

"It is exciting to observe dose-related efficacy signals in certain solid tumors and lymphomas, and in particular endometrial cancer and T-cell lymphoma," noted Mark Kirschbaum M.D., Senior Vice President and Chief Medical Officer. "Based on the absence of dose-limiting toxicities at all dose levels, we are adding two dose levels in a protocol amendment to test higher doses of oral fadraciclib before determining the recommended Phase 2 dose which we anticipate in the second half of 2022."

1H 2022 Key Achievements and Corporate Updates

Fadraciclib

Fifteen patients with advanced solid tumors and lymphomas treated with oral fadraciclib at all five dose levels as per protocol in the 065-101 dose escalation study.
Demonstrated evidence of target engagement for CDK2 and CDK9 in cell assay system and patient PK data suggested that these targets are potentially inhibited at 100mg twice daily levels.
A cutaneous T cell lymphoma (CTCL) patient achieved partial response (PR) in the first oral treatment cycle.
A peripheral T cell lymphoma (PTCL) patient achieved 38% reduction in target lesions by PET scan in the first oral treatment cycle.
An endometrial cancer patient achieved stable disease with 15% reduction of target lesions after the first oral treatment cycle. In an earlier study of intravenous fadraciclib as monotherapy, a patient with MCL1 amplified endometrial cancer achieved confirmed complete response (CR) and remains on study after two and a half years of treatment.
A pancreatic cancer patient achieved stable disease by confirmatory scan for five oral treatment cycles.
As no dose limiting toxicities have been observed, the Company has submitted a protocol amendment to the U.S. Food and Drug Administration (FDA) to escalate to two additional dose levels before determining recommended Phase 2 dose (RP2D).
Based on good tolerability in 065-101, a protocol amendment in the 065-102 study of oral fadraciclib in patients with leukemia or myelodysplastic syndromes has enabled acceleration of the study by omitting dose levels two and three and now enrolling at dose level 4.
CYC140

No dose limiting toxicities observed to date in 140-101, a Phase 1/2 study of oral CYC140 in solid tumors.
An ovarian cancer patient in 140-101 achieved stable disease with tumor shrinkage after the first cycle.
Corporate Updates

The Company is planning an R&D Day in the fall of 2022 to present updated data from the 065-101 and 140-101 clinical trials.
The Company has also submitted an abstract to potentially present fadraciclib data from 065-101 at a cancer conference in the fall of 2022.