6-7 - News

Lilly and Precision will collaborate on the research and development of in vivo therapies for gene disorders, with an initial focus on Duchenne muscular dystrophy and two further undisclosed gene targets.

Precision’s ARCUS genome editing platform could deliver ‘safer, more specific gene edits’ through the use of a naturally occurring gene editing enzyme known as endonuclease I-CreI, according to the company.

By using this technology, Precision can re-engineer the enzyme’s editing abilities to ‘knock-in, knock-out and repair’ the targeted cells.

“We look forward to working with Lilly to leverage our deep understanding of in vivo gene editing and experience with ARCUS to develop new therapies, including a potentially transformative treatment for Duchenne muscular dystrophy,” said Derek Jantz, chief scientific officer and co-founder of Precision BioSciences.

Under the terms of the deal, Lilly will pay Precision $100m upfront and also make an equity investment totalling $35m in Precision’s common stock.

In addition, Precision is eligible to receive up to $420m in potential development and commercialisation milestones per product, with tiered royalties on top of that if Lilly successfully commercialises a therapy from the collaboration.

While Precision will lead preclinical research and IND-enabling activities, Lilly will assume responsibility for clinical development and commercialisation.

Sanofi’s Supemtek is the now first and only recombinant influenza vaccine to be approved within the European Union.

The French pharma giant developed Supemtek using recombinant technology, which allows an exact match to the key component of the flu strains recommended by the World Health Organization (WHO).

The EU approval is based on data from two phase 3 clinical trials involving over 10,000 participants in total. When evaluated in these trials, Supemtek reduced the risk of flu by an additional 30% in adults aged 50 years and older compared to a standard-dose egg-based quadrivalent influenza vaccine.

Global influenza-associated deaths range from between 290,000 to 650,000 each year, with around ten million influenza-related hospitalisations also reported every year.
Sanofi expects the first European launches of Supemtek for the 2022/2023 flu season and a possible fast-track of doses to be delivered by the 2021/2022 season in certain countries.
Sanofi is also utilising its recombinant technology to develop a COVID-19 vaccine, which will be combined with an adjuvant from GlaxoSmithKline (GSK).

Earlier this year, the European Commission approved Recarbrio (imipenem/cilastatin/relebactam) for the treatment of infections caused by aerobic Gram-negative organisms in adults with limited treatment options. The regimen combines MSD’s imipenem/cilastin duo with a new beta lactamase inhibitor called relebactam that is designed to restore susceptibility to imipenem in resistant strains.
In a pivotal phase 3 trial of adult patients with infections caused by imipenem-nonsusceptible Gram-negative bacteria, Recarbrio was comparable to the combination of imipenem/cilastatin plus colistin: 71% and 70%, respectively.

Colistin is a drug which was first introduced in the 1950s that has been resurrected to help fight challenging Gram-negative infections. The result was particularly significant, given that colistin is often reserved as a ‘last-line’ therapeutic for Gram-negative infections, although the drug can have significant side effects including kidney damage.
According to the World Health Organization (WHO), at least 700,000 people die each year worldwide because of drug-resistant infections.

Despite the urgent need for new therapeutics to tackle the growing incidence of antimicrobial resistance (AMR), few pharmaceutical companies are undertaking research in this area.

This is mainly due to the fact that when new antibiotics are launched, they are often held in reserve and used only to treat the most resistant infections.

Earlier this year, the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) raised nearly $1bn to support clinical research into new antibiotics in a bid to tackle AMR.

The aptly named AMR Action Fund is aiming to bring two to four new antibiotics to patients by 2030. The launch of the fund resulted from a collaboration between 20 biopharmaceutical companies, including MSD, the European Investment Bank (EIB), Wellcome Trust and the WHO.

Belgium-headquartered UCB has strengthened its gene therapy capabilities with a pair of deals – a collaboration agreement with Lacerta Therapeutics and the acquisition of Handl Therapeutics.

Handl Therapeutics – based in Leuven, Belgium – specialises in adeno-associated virus (AAV) capsid technology and has a focus on developing disease-modifying gene therapies to treat neurodegenerative diseases.

In addition to its own capabilities, Handl has built an international network to access expertise from a number of institutions. This includes platforms licensed from KU Leuven in Belgium, the Centre for Applied Medical Research in Spain, the University of Chile and King’s College London in the UK.

UCB did not disclose the financial terms of the acquisition, although it did add in a statement that the Handl team will continue to be based in Handl and will work closely with UCB’s international research team.

The Lacerta deal is focused on developing AAV-based therapies for patients with ‘a central nervous system disease with a high unmet need’. Like the Handl acquisition, UCB did not offer the financial details of the Lacerta research collaboration and licensing agreement.
Lacerta is set to lead research and preclinical activities as well as the early manufacturing process development, with UCB planning to lead IND-enabling studies, manufacturing and clinical development.

The Handl and Lacerta deals build on UCB’s previous acquisition of Element Genomics in 2018.

French pharma group Pierre Fabre’s Braftovi has been recommended for NHS use by the UK’s National Institute for Health and Care Excellence (NICE) to treat BRAF-positive colorectal cancer.

Braftovi (encorafenib) combined with Merck KGaA’s EGFR-targeting antibody Erbitux (cetuximab) has been recommended as a second-line treatment for BRAF-positive metastatic colorectal cancer (mCRC).

The positive recommendation is based on results from the phase 3 BEACON CRC study, in which Braftovi/Erbitux significantly improved overall survival (OS) by 40% compared to Erbitux and irinotecan-based chemotherapy, with a median OS of 9.3 months and 5.9 months respectively.

The trial also demonstrated that the treatment combinations was as effective as a triple therapy which also included Mektovi (binimetinib), which meant that additional toxicity from the MEK inhibitor could be avoided without comprising patient benefit.

Pierre Fabre is also looking to prove the Braftovi/Mektovi combination in earlier patient settings – the phase 2 ANCHOR CRC trial is evaluating the drug combo plus Erbitux or another EGFR inhibitor as a chemotherapy-free option for mCRC patients.

Results from this study demonstrated that the three-drug treatment produced a confirmed objective response rate (cORR) of 50%, with tumour-size reduction observed in 85% of patients. In addition, the investigator-measured median progression-free survival (PFS) rate was 4.9 months.

Over 42,000 people in the UK are newly diagnosed with colorectal cancer each year, with approximately 8-12% of patients with mCRC also carrying BRAF mutations.

The US Food and Drug Administration (FDA) has delayed a crucial decision for Bristol Myers Squibb’s CAR-T therapy liso-cel, a key asset gained in the company’s Celgene acquisition.

BMS picked up liso-cel (lisocabtagene maraleucel) following its $74bn takeover of Celgene last year – the CAR-T therapy is one of the key assets critical to the potential payout of the merger in contingent value rights (CVR).

As part of the merger agreement, BMS agreed on a series of conditional payments to former Celgene shareholders or CVR holders, contingent on the regulatory approval of liso-cel by 31 December 2020, totalling an extra $6bn.

BMS also agreed similar conditional payments, dependent on approval, for Celgene’s multiple sclerosis therapy Zeposia (ozanimod) and another CAR-T therapy, ide-cel (idecabtagene vicleucel).

Zeposia was approved earlier this year, while ide-cel’s deadline is coming up in March 2021.

In February, the FDA kick-started a priority review of liso-cel for the treatment of relapsed/refractory large B-cell lymphoma for patients who have received at least two prior therapies.

The CAR-T therapy targets CD19, a protein which is highly expressed on the surface of B cells and remains following the transformation of these cells from normal to malignant.
The FDA biologics licence application (BLA) is based on results from the TRANSCEND NHL–1 study, in which liso-cel achieved a 53% complete response rate and an overall response rate of 73% in the patient population.

However, the FDA has now postponed its decision on liso-cel after it was unable to complete an inspection of a third-party manufacturing facility in the US, which is involved in making a component of the CAR-T therapy.

The agency blamed its inability to conduct the inspection on travel restrictions related to the COVID-19 pandemic and declined to provide a new anticipated action date for the liso-cel decision.

Lilly links up with Precision BioSciences in genome editing deal

Sanofi’s quadrivalent flu vaccine Supemtek scores EU approval

MSD launches antibiotic combo Recarbrio in UK

UCB boosts gene therapy offering with a pair of new deals

Pierre Fabre’s Braftovi scores NICE backing for BRAF+ colorectal cancer

FDA delays BMS’ liso-cel decision, citing COVID-19 travel restrictions