Pharmaceutical Technology Editors

Takeda announced its intent to acquire NDI-034858, an oral, selective allosteric tyrosine kinase 2 (TYK2) inhibitor, from Nimbus Pharmaceuticals, a clinical-stage drug discovery company, on Dec. 13, 2022. Takeda plans to purchase the drug, which is being evaluated for treatment in various autoimmune diseases, for a total of $6 billion. Four billion dollars will be paid upfront, with Nimbus also eligible for two milestone payments of an additional billion dollars when the drug achieves annual net sales of $4 billion and $5 billion, respectively.

According to a company press release, Nimbus recently disclosed positive topline results from a Phase IIb study evaluating NDI-034858 in patients with moderate-to-severe plaque psoriasis. It is expected to enter Phase III for psoriasis in 2023, and the drug is also in an ongoing Phase IIb study in active psoriatic arthritis. Additionally, Takeda also plans to investigate it for treatment of inflammatory bowel disease and other autoimmune diseases.

“Adding this TYK2 inhibitor to our late-stage pipeline gives Takeda an exciting program that has the potential to significantly expand our portfolio and patient impact, while enhancing our growth strategy beyond [vedolizumab],” said Christophe Weber, president and CEO, Takeda, in the release. “We are confident we can execute a broad development program and deliver a best-in-class therapy for these patients, given Takeda’s strong background in immune-mediated diseases, including inflammatory bowel disease.”

“This program further expands Takeda’s GI [gastrointestinal] clinical programs and therapeutic focus. After having seen the NDI-034858 Phase [IIb] data, particularly the [psoriasis area and severity index] scores, we are excited by the differentiation of this molecule within the TYK2 class, and we believe in its broad potential for people with autoimmune diseases,” said Andy Plump, president of R&D, Takeda, in the release. “By virtue of its unique allosteric mechanism of action, NDI-034858 is both a potent and highly selective TYK2 inhibitor with exceptional clinical activity, a strong tolerability profile, and wide therapeutic margins. NDI-034858 is a potentially best-in-class TYK2 inhibitor across a wide range of immune mediated conditions.”

Following the acquisition, NDI-034858 will be known as TAK-279. A closing date was not disclosed and is contingent on completion of review under antitrust laws.

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Takeda will purchase the rights to Nimbus Pharmaceuticals candidate, NDI-034858, which is currently being evaluated for treating multiple autoimmune diseases.

Takeda to Purchase Autoimmune Treatment for $6 Billion

The European Commission (EC) permitted a conditional marketing authorization for Boehringer Ingelheim’s Spevigo (spesolimab) as a first-in-class treatment for generalized pustular psoriasis (GPP) flares in adults.

Spevigo is a novel, selective antibody that blocks the activation of the interleukin-36 receptor (IL-36R), a signaling pathway within the immune system shown to be involved in the pathogenesis of GPP.

“The symptoms of GPP are devastating and cause immense pain as well as hospitalization during a flare. Increased GPP awareness that leads to accurate and faster diagnosis is one important step to improving the quality of life for people living with GPP,” said Frida Dunger Johnsson, executive director, IFPA, in a press release. “Now with a specifically developed treatment, people living with GPP can be offered a new lease of life by effectively managing the impact of GPP flares.”

The approval is based on results from the pivotal EFFISAYIL 1 Phase II clinical trial. In the 12-week trial, patients who experiencing a GPP flare were treated with Spevigo or placebo, and most patients at the outset of the trial had a moderate or severe pustulation of the skin.

In a week duration’s time, 54% of patients treated with a single dose of Spevigo showed no visible pustules compared to placebo. In 66% of patients treated with Spevigo, adverse events (AEs) were reported, whereas 56% of patients receiving placebo reported AEs after one week.

Infections in patients were reported by 17% and 6% of patients in the Spevigo and placebo groups, respectively, and serious AEs were reported in 6% of patients treated with Spevigo.

European Commission approves SPEVIGO® (spesolimab) for generalized pustular psoriasis flares. 

https://www.boehringer-ingelheim.com/human-health/skin-diseases/gpp/european-commission-approves-spevigo-spesolimab-generalized

The approval is based on results from the pivotal EFFISAYIL 1 Phase II clinical trial.

European Commission Approves Spevigo for Generalized Psoriasis Flares

Moderna received emergency use authorization (EUA) from FDA for its BA.4/BA.5 Omicron-targeting bivalent COVID-19 booster vaccine, mRNA-1273.222 in children six months to five years of age.

The authorization is based on a 10 μg booster dose following a completed primary series of Moderna’s original vaccine. Additionally, the booster dose of mRNA-1273.222 contains messenger RNA (mRNA) encoding for the spike protein of BA.4/BA.5 and mRNA encoding for the original strain of the SARS-CoV-2 virus.

"With the FDA's decision, children and adolescents of all age groups in the US will now be eligible for our updated bivalent COVID-19 booster, providing families with an important protective tool as we continue through the winter months," said Stéphane Bancel, chief executive officer of Moderna, in a press release. "We appreciate the FDA's timely review."

mRNA-1273.222 has also received FDA EUA for children and adolescents between six and 17 years of age and for adults over the age of 18 years of age.

The pediatric EUA application is based on clinical trial booster data for Moderna’s original vaccine, Spikevax. This also included pre-clinical data for mRNA-1273.222 and from a Phase II/III studying mRNA-1273.214, which is another Omicron-targeting bivalent booster vaccine created by Moderna.

Moderna recently announced results from a Phase II/III trial in more than 500 adults, which highlighted that mRNA-1273.222 induced significantly higher neutralizing antibody titers against BA.4/BA.5 versus a booster dose of Moderna’s original vaccine.

Currently, a Phase II/III trial evaluating Omicron-targeting bivalent vaccines as booster and primary series in children between six months and five years of age has begun, with preliminary results expected in early 2023.

Moderna Receives FDA Emergency Use Authorization For Omicron-Targeting Bivalent COVID-19 Booster Vaccine In Children 6 Months Through 5 Years Of Age. 

https://investors.modernatx.com/news/news-details/2022/Moderna-Receives-FDA-Emergency-Use-Authorization-for-Omicron-Targeting-Bivalent-COVID-19-Booster-Vaccine-in-Children-6-Months-Through-5-Years-of-Age/default.aspx

Moderna Receives FDA Emergency Use Authorization for Omicron-Targeting Bivalent COVID-19 Booster Vaccine in Children 

Generate Biomedicines, a pharmaceutical company based in the United States focused on protein generative platforms, recently published a preprint describing technology capable of generating novel proteins. The technology, enabled via their machine learning (ML) model, Chroma, is designed to tailor these proteins toward desired functional or other properties.

According to a company press release from Dec. 1, 2022, this program aims to aid the design of novel therapeutics and bring new medicines to patients faster, cheaper, and better tailored to specific conditions. Additionally, because Chroma learns from each new protein it produces and validates, the company believes the platform has the potential to scale therapeutic development to a degree previously unseen.

“We believe our model will have revolutionary implications. It is akin to learning how to ‘write’ in the mysterious language of proteins. Now that we have this ability, the possibilities of what we can produce are endless,” said Gevorg Grigoryan, co-founder and chief technology officer, Generate Biomedicines, in the release. “The transition from conventional drug discovery to generative biology will mean that we no longer discover suboptimal medicines that nature evolved for its own purposes; instead, we will be creating, or generating, purpose-built, highly efficacious medicines.”

Additionally, the company stated that the manuscript for the technology will be for peer-review and the preprint submitted to bioRxiv.org.

Generate Biomedicines published a preprint describing technology that can generate novel proteins towards desired functional or other properties.

Generate Biomedicines Uses AI to Create Proteins That Have Never Existed

PictorLabs, a Los Angeles-based digital pathology company developing an artificial intelligence (AI)-powered virtual staining platform, formally announced its launch at the start of December 2022. The company launched with more than $18.8 million in funding since its founding in 2019.

According to a Dec. 1, 2022 press release, the company’s technology is designed to apply deep learning algorithms to efficiently and accurately stain tissues 

, producing near-instantaneous virtual stains. From a single unstained tissue sample, PictorLabs’ proprietary platform can produce an unlimited number of virtual stains that are indistinguishable from analogous chemical stains. This eliminates the need for chemical staining, reduces the time to results, and allows for repeated biomarker testing without the need for multiple tissue samples.

PictorLabs has also demonstrated successful virtual staining for several well-validated disease biomarkers, according to the press release. The company is now pursuing additional opportunities in disease areas with high unmet need. The company plans to use its latest round of funding to expand its biomarker portfolio, develop novel products, grow the company’s talent base, and build out its corporate infrastructure.

“PictorLabs’ platform overcomes inherent issues in histopathology through the application of AI-powered algorithms that produce virtual stains which are indistinguishable from their chemistry-based counterparts,” said Yair Rivenson, CEO and chief technology officer, PictorLabs, in the press release. “By virtually staining tissue images in the digital realm, our approach simplifies and accelerates workflows, speeding up drug discovery and diagnostic decision-making with the goal of ultimately improving patient outcomes. With the support of our experienced investors, we’re now well placed to systematically expand our platform.”

PictorLabs, a digital pathology company developing an AI-powered virtual staining platform, formally announced its launch at the start of December.

Virtual Staining Start-Up Launches with More Than 18.8 Million in Funding

FDA has published a draft guidance on Dec. 5, 2022, with recommendations to sponsors and applicants who intend to use equivalence criteria in analyzing 

 bioequivalence (BE) studies for investigational new drug applications, new drug applications, abbreviated new drug applications, and supplements to these applications.

The guidance discusses statistical approaches for BE comparisons and focuses on how to use these approaches both generally and in specific situations. After being finalized, it will replace the Guidance for Industry, 

Statistical Approaches to Establishing Bioequivalence

, which was originally issued in February 2001.

In addition to covering some of the topics in the 2001 guidance, subjects discussed in the new guidance will include missing data, intercurrent events, narrow therapeutic index drugs, variable drugs, and data preparation.

The draft guidance can be viewed in full 

The guidance discusses statistical approaches for BE comparisons and focuses on how to use these approaches both generally and in specific situations.