Pharmaceutical Technology Editors

Todos Medical, a medical diagnostics company, announced that its lab, Provista Diagnostics, has successfully completed the validation studies required to put its cPass neutralizing antibody blood test into production. The company expects to launch the new test in September 2021, and Provista Diagnostics can do up to 20,000 polymerase chain reaction tests and over 1500 cPass tests per day, according to a company press release.

The blood test received Emergency Use Authorization from FDA for the detection of neutralizing antibodies (NAbs) that could be used to monitor key biomarkers of COVID-19. Individuals who acquired their immunity through either vaccination or natural infection will be able to monitor their immunity levels with the device.

This product comes on the heels of breakthrough infections in vaccinated individuals and discussions surrounding whether booster shots are necessary. FDA recently sent out a recommendation advising immunocompromised individuals to consider a third shot.

“We saw our local community in the greater Atlanta area ravaged by the first and second waves of the disease due to a lack of testing capability, and felt we had an obligation to be more proactive to fulfill the market need just as schools and business prepare to open for the fall.” said Gerald Commissiong, president & CEO of Todos Medical, in the press release. “We think cPass could play a pivotal role in helping roll out booster shots to those at-risk in the months ahead.

Articles

Todos Medical has completed validation of its cPass neutralizing antibody blood test to monitor COVID-19 immunity.

Todos Medical to Launch New Antibody Blood Test for COVID-19

NGM Biopharmaceuticals, a US-based biotechnology company, disclosed a fourth oncology development candidate on Aug. 23, 2021. The new candidate, NGM831, is an antagonist antibody designed to block the interaction between immunoglobulin-like transcript 3 (ILT3) and fibronectin, as well as other ligands.

NGM Bio plans to initiate first-in-human testing of the candidate in the first half of 2022. The company started a Phase I/II study of a previous candidate, NGM707, in July 2021 to investigate (the efficacy/safety or both?) that candidate when administered solo or in combination with KEYTRUDA (pembrolizumab) in patients with advanced solid tumors. The company also plans to initiate a Phase I study of another previous candidate, NGM438, in advanced solid tumors in the first half of 2022.

The announcement of the fourth oncology candidate coincides with a paper published in 

, a journal of the American Association for Cancer Research (1) that described the discovery of fibronectin, a functional ligand for ILT3, and an extracellular matrix protein that forms a fibrillar network within the tumor stroma. According to the publication, ILT3 is a fibronectin-binding inhibitory immune receptor that receives signals from the extracellular matrix causing it to directly promote myeloid cell suppression. ILT3 is expressed specifically on tumor-associated myeloid cells, and particularly high expression has been found on tolerogenic dendritic cells (DCs), myeloid-derived suppressor cells, and M2 macrophages.

This discovery enabled NGM Bio to develop NGM831, which is expected to reprogram tolerogenic DCs into stimulatory cells by enhancing fragment crystallizable region receptor activity. The candidate is also expected to enhance T cell infiltration and activation. In addition to this fourth candidate, NGM Bio’s oncology portfolio includes NGM120 (anti-GFRAL), NGM707 (anti-ILT2/ILT4), and NGM438 (anti-LAIR1).

“The work we published on the ILT3–fibronectin pathway and our unveiling of NGM831 is yet another proof point of our robust in-house capabilities to deeply interrogate biology and rapidly translate our discoveries into investigational medicines designed to bring hope and meaningful change to patients with cancer and other serious diseases,” said David J. Woodhouse, CEO of NGM Bio, in a company press release. “With oncology programs now targeting ILT2/ILT4, ILT3, and LAIR1 [leukocyte associated immunoglobulin-like receptor 1], we have constructed a comprehensive myeloid reprogramming strategy that is directed at multiple and distinct targets. Our planned biomarker strategy across the NGM707, NGM831, and NGM438 clinical development programs will help inform target patient populations for each product candidate.”

“NGM [Bio] has a strong track record of identifying important ligand-receptor interactions, thereby opening the door to impactful therapeutics,” said Alex DePaoli, chief translational officer at NGM Bio, in the press release. “We are pleased to showcase how our team of scientists identified ILT3’s functional ligand, fibronectin, and subsequently designed an antibody specifically tailored against the target. By inhibiting ILT3’s interaction with fibronectin, NGM831 represents another potential approach to mobilize a patient’s own immune system to fight tumors by shifting myeloid cells from a suppressive state to a stimulatory state and promoting antitumor immunity.”

NGM Biopharmaceuticals has disclosed a fourth antibody drug candidate, NGM831, for development into an oncology therapeutic.

NGM Bio Pinpoints Fourth Antibody Drug Candidate for Oncology Therapy Development

Pfizer announced on Aug. 23, 2021 that it will acquire Trillium Therapeutics, a Massachusetts-based clinical-stage immuno-oncology company in a deal worth $2.26 billion. The acquisition will add two lead molecules in development for treating hematological malignancies (e.g., blood, bone marrow, and lymph node cancers) to Pfizer’s oncology pipeline.

Under the agreement, Pfizer will acquire all outstanding shares of Trillium that it does not already own for $18.50 per share, an implied equity value of $2.26 billion, in cash. The transaction price represents a 118% premium to the 60-day weighted average price for Trillium, according to a company press release.

Trillium’s portfolio consists of biologics designed to enhance the innate ability of the immune system to detect and destroy cancer cells. The two lead molecules, TTI-622 and TTI-621, block the signal-regulatory protein α (SIRPα)–CD47 axis, which has shown to be a key immune checkpoint in hematological malignancies. TTI-622 and TTI-621 are novel SIRPα-Fc fusion proteins currently in Phase Ib/II development across several hematological malignancy-related indications.

TTI-622 and TTI-621 have demonstrated in clinical studies to-date activity as a monotherapy option in relapsed or refractory lymphoid malignancies, including diffuse large B-cell lymphoma, peripheral T-cell lymphoma, follicular lymphoma, and other lymphoid malignancies. The two molecules are currently the only known CD47-targeted molecules that have demonstrated meaningful single-agent activity and complete responses in multiple hematological malignancies.

“We are encouraged by the early clinical data for TTI-622 and TTI-621 monotherapy for patients with heavily pretreated lymphoid malignancies and early encouraging activity for TTI-622 in patients with multiple myeloma. Just as PD-1 [programmed cell death protein 1] and PD-L1 [programmed cell death ligand 1] blockers have proven to be effective immuno-therapeutics for many solid tumors, the SIRPα-CD47 interaction defines a second key immune checkpoint for which disrupting agents are expected to become another important backbone immunotherapy for multiple types of cancer, especially hematological cancers,” said Chris Boshoff, chief development officer, Oncology, Pfizer Global Product Development, in the press release. “Utilizing Pfizer’s leading research and global development capabilities, we plan to accelerate the clinical development of SIRPα fusion proteins as a potential new scientific breakthrough and explore combinations within our own portfolio and with innovative next-generation medicines for hematological malignancies.”

“The proposed acquisition of Trillium builds on our strong track record of leadership in Oncology, enhancing our hematology portfolio as we strive to improve outcomes for people living with blood cancers around the globe. Our deep experience in understanding the science of blood cancers, along with the diverse knowledge base we have developed across our growing hematology portfolio of eight approved and investigational therapies, provide us with a foundation to advance these important potential medicines to patients who need them,” said Andy Schmeltz, global president and general manager, Pfizer Oncology, in the press release.

“Trillium has the only known SIRPα–CD47 targeting molecules with clinically meaningful monotherapy responses as well as a strong basis for combination therapies, which is supported by preclinical evidence with a diverse set of therapeutic agents. With Pfizer’s global reach and deep capabilities, we believe our programs will advance more quickly to the patients we’ve always aspired to serve. We believe this is a good outcome for patients and our shareholders,” said Jan Skvarka, CEO of Trillium, in the press release.

Pfizer’s proposed $2.26-billion acquisition of Trillium Therapeutics will add next-generation hematology-targeted immuno-therapeutics to its oncology pipeline.

Pfizer to Acquire Trillium Therapeutics in $2.26-Billion Deal

Lonza announced on Aug. 23, 2021 that it is further investing in its new 17,000-m

 current good manufacturing practice (CGMP) mammalian facility in Guangzhou, China, to establish drug product manufacturing capabilities. As part of the new investment, the company will install an aseptic drug product fill/finish production line. The Guangzhou facility began operations in the second quarter of 2021, and Lonza expects to deliver its first CGMP batch later this year.

The installation of the aseptic fill/finish production line will supply global and domestic customers with clinical trial material and commercial batches in China and will support the filling of liquid and lyophilized products. Installation of this line is expected to be complete in 2022.

The addition of drug product manufacturing at the Guangzhou site will result in integrated drug substance and drug product manufacturing services. To facilitate the installation of the drug product manufacturing line, Lonza will also expand its global drug product services hub in Basel, Switzerland. The Basel hub provides formulation development and process development to support drug product capabilities across the company's global network.

"The investment in drug product manufacturing capabilities at Lonza Guangzhou not only demonstrates our commitment to the Chinese market but also marks an important milestone in achieving our long-term ambition of increasing drug product capacity and addressing growing customer demand for an end-to-end drug product solution. Through the expansion of our services at Lonza Guangzhou, we will have the capability to support our customers with the late-stage clinical trial and commercial development of potentially life-saving treatments," said Hong Pan, general manager, China, Lonza, in a company press release.

"The future expansion of our Drug Product Services in Basel will be a key enabler to support our integrated drug substance and drug product offering across modalities. Combined with the planned expansion of development services in Basel, the new drug product manufacturing line in China will allow us to extend our best-in-class offering to meet increasing customer demand," added Peter Droc, head of Drug Product Services, Lonza, in the press release.

Lonza plans to establish drug product manufacturing capabilities at is site in Guangzhou, China, to produce clinical trial and commercial supply in the country.

Lonza Invests in Drug Product Manufacturing Services in China

FDA announced the availability of a draft guidance, “Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs Submitted Under an ANDA,” on August 20, 2021, which provides recommendations to applicants planning to include bioequivalence (BE) information in abbreviated new drug applications (ANDAs) and ANDA supplements. Specifically, the guidance:

Describes how to meet the BE requirements set forth in FDA regulations

Is applicable to dosage forms intended for oral administration and to non-orally administered drug products in which reliance on systemic exposure measures is suitable for documenting BE

Will be useful when planning BE studies conducted during the post-approval period for certain changes in an ANDA

In general, applicants for ANDAs must use an approach that is the most accurate, sensitive, and reproducible, according to the draft guidance. The draft guidance also says that 

 methods can be used to establish BE. Specifically, the draft guidance covers:

Establishing BE (including pharmacokinetic studies)

Establishing BE for different dosage forms (including oral solutions, immediate-release products, such as capsules and tablets, suspensions, modified-release products, chewable tablets, orally-disintegrating tablets, sublingual, and transdermal)

Alcoholic beverage effects on modified-release drug products

FDA’s draft guidance provides recommendations for how to include bioequivalence information in ANDAs and ANDA supplements. 

FDA Offers Guidance on How to Include Bioequivalence Info in ANDAs

On August 18, 2021, the US Department of Health and Human Services (HHS) Public Health and a team of medical experts produced a statement on COVID-19 booster shots, saying that the COVID-19 vaccines authorized in the United States are effective, but that a booster shot will be needed to maximize vaccine-induced protection and prolong its durability. Starting in September 2021, the officials hope to begin administering booster shots to individuals who received their second dose eight months ago—pending an FDA evaluation and Centers for Disease Control and Prevention’s (CDC’s) issuing booster dose recommendations.

The HHS Public Health and the team of medical experts said in the statement that the COVID-19 vaccines are effective in reducing the risk of severe disease, hospitalization, and death—including against the Delta variant. However, as HHS Public Health and the team of medical experts study the scientific data surrounding the pandemic, they have found that protection against the SARS-CoV-2 infection decreases over time following the initial doses of vaccination. They also note that many vaccines (outside of the COVID-19 vaccine) have a reduction in protection over time, and additional vaccine doses may be needed to provide long-lasting protection.

“Based on our latest assessment, the current protection against severe disease, hospitalization, and death could diminish in the months ahead, especially among those who are at higher risk or were vaccinated during the earlier phases of the vaccination rollout,” said HHS Public Health and a team of medical experts in the statement. “For that reason, we conclude that a booster shot will be needed to maximize vaccine-induced protection and prolong its durability.”

According to this statement, HHS Public Health and the team of medical experts have developed a plan to offer COVID-19 booster shots this fall, starting September 20, 2021. Individuals will receive the booster shot eight months after their second dose. This plan is dependent upon:

FDA conducting an independent evaluation and determination of the safety and effectiveness of a third dose of the Pfizer and Moderna messenger RNA vaccines

CDC’s Advisory Committee on Immunization Practices issuing booster dose recommendations

The statement is attributed to Rochelle Walensky, director, CDC; Dr. Janet Woodcock, acting commissioner, FDA; Vivek Murthy, US surgeon general; Dr. Francis Collins, director of the National Institutes of Health; Anthony Fauci, chief medical advisor to President Joe Biden and director of the National Institute of Allergy and Infectious Diseases; Rachel Levine, assistant secretary for Health; David Kessler, chief science officer for the COVID-19 response; and Marcella Nunez-Smith, chair of the COVID-19 Health Equity Task Force.

HHS Public Health and a team of medical experts recommend that COVID-19 vaccine booster shots will soon be necessary. 