Bristol Myers Squibb (BMS) and GentiBio have announced a multi-year partnership to develop new regulatory T-cell (Treg) therapies to re-establish immune tolerance and repair tissue in patients living with inflammatory bowel diseases (IBD).

BMS has made an undisclosed upfront cash payment to GentiBio. GentiBio is also eligible to receive development and sales milestone payments of up to $1.9bn and royalties. As part of the agreement, BMS will have the right to develop and advance up to three of the resulting programmes into clinical trials.

BMS will use its experience in cell therapies and immunology along with GentiBio’s modular-engineered Treg platform and scalable manufacturing process to produce stable and disease-specific engineered Tregs for use against multiple targets.

IBD, a term mainly used to define ulcerative colitis and Crohn’s disease, is characterised by debilitating and life-threatening chronic inflammation of the gastrointestinal tract (GI). There is currently no cure for ulcerative colitis or Crohn’s disease, and the majority of current therapies are focused on systemic anti-inflammatory agents and broad immunosuppression, which can result in adverse effects outside the GI tract.

As a specialised subpopulation of T cells that act to suppress immune response, Tregs have been shown to inhibit T-cell proliferation and cytokine production and are thought to play a critical role in preventing autoimmunity.

Merck – known as MSD outside the US and Canada – and Orna Therapeutics (Orna) have announced a collaboration agreement to advance Orna’s next generation of RNA technology.

Under the terms of the agreement, Merck will make an upfront payment of $150m to Orna.

In addition to this, Orna will also be eligible to receive up to $3.5bn in milestones, as well as royalties.

Orna will retain rights to its oRNA-LNP technology platform and will continue to advance other wholly owned programmes in areas such as oncology and genetic diseases. Merck will also invest $100m in Orna’s recently completed series B financing round.

Aiming to discover, develop and commercialise multiple programmes, including vaccines and therapeutics in the areas of infectious disease and oncology, the collaboration will see Merck partner with Orna on its proprietary circular RNA (oRNA) technology.

oRNA molecules have demonstrated greater stability in vivo compared to linear mRNA and can potentially produce larger amounts of therapeutic proteins inside the body.

The molecules can also be packaged into lipid nanoparticles, which Orna has engineered to target key tissues in the body.

Preclinical data showed the potential of oRNA expression and delivery as an approach for further development in various areas, including vaccines and oncology treatments.

The announcement comes after Merck and Cerevance signed a multi-year strategic research collaboration agreement to identify novel targets for Alzheimer’s disease.

AstraZeneca (AZ) and Daiichi Sankyo have shared positive results from a phase 3 trial for Enhertu (trastuzumab deruxtecan) to treat patients with HER2-positive metastatic breast cancer.

The 600-patient phase 3 DESTINY-Breast02 trial compared Enhertu to a treatment given by doctors to people with HER2-positive metastatic breast cancer.

The trial evaluated a similar breast cancer patient population as the DESTINY-Breast01 phase 1 trial, which was the basis for initial approvals in Europe and several other countries, AZ said.

DESTINY-Breast02 demonstrated a ‘statistically significant and clinically meaningful improvement in progression-free survival’ in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab emtansine.

The trial also met the key secondary endpoint of improved overall survival, and the safety profile of Enhertu was consistent with previous phase 3 clinical trials, with no new safety concerns identified.

Enhertu belongs to a class of therapies called antibody drug conjugates and consists of a HER2 monoclonal antibody chemically linked to a cell-killing chemotherapy drug.

The announcement follows the approval of Enhertu by the US Food and Drug Administration to treat adults with unresectable or metastatic breast cancer expressing low levels of HER2, a newly defined subset of HER2-negative breast cancer.

Celltrion Healthcare’s Vegzelma has been approved by the European Commission (EC) for the treatment of multiple types of cancer, the company announced.

Vegzelma has been approved specifically for the treatment of metastatic breast cancer, non-small cell lung cancer (NSCLC), advanced and/or metastatic renal cell cancer, metastatic carcinoma of the colon or rectum, ovarian cancer and cervical cancer.

Vegzelma is a recombinant humanised monoclonal antibody treatment biosimilar to Genentech’s Avastin (bevacizumab), which is approved in the EU.

By attaching to vascular endothelial growth factor, Vegzelma hinders VEGF binding to its receptors Flt-1 and kinase insert domain receptor on the endothelial cell surface.
Biosimilars have no clinically significant differences in terms of safety or effectiveness from the reference product, but they have potentially lower costs.

The EC approval is based on the ‘totality of evidence’, including a phase 3 pivotal trial in patients with metastatic or recurrent non-squamous NSCLC, which demonstrated that Vegzelma – as a first-line treatment – is highly similar to Avastin.

The approval follows the recommendation for marketing authorisation issued by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) in June this year.

Vegzelma marks Celltrion’s third oncology biosimilar to receive regulatory approval in the EU, following Truxima (biosimilar to rituximab) and Herzuma (biosimilar to trastuzumab).

Gilead Sciences (Gilead) has announced positive results from a phase 3 study evaluating Trodelvy for metastatic breast cancer patients.

The study was evaluating Trodelvy (sacituzumab govitecan-hziy) in pre-treated hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer patients.

HR+/HER2- breast cancer is the most common type of breast cancer, accounting for around 70% of all new cases, or nearly 400,000 diagnoses worldwide each year.

As patients with HR+/HER2- metastatic breast cancer become resistant to endocrine-based therapy, their primary treatment option is limited to single-agent chemotherapy.

The company also announced an agreement with Everest Medicines to transfer all development and commercialisation rights to Gilead for Trodelvy in Greater China, South Korea, Singapore, Indonesia, Philippines, Vietnam, Thailand, Malaysia and Mongolia.

Under the terms of the agreement, Gilead will make a $280m upfront payment to Everest, who is eligible to receive up to $175m in potential milestones.

The phase 3 study demonstrated ‘statistically significant’ results from the second interim analysis of the key secondary endpoint of overall survival in patients who had received prior endocrine therapy, CDK4/6 inhibitors and two to four lines of chemotherapy.

Additionally, the safety profile for Trodelvy was consistent with prior studies, and no new safety signals were observed. Gilead has submitted a supplemental Biologics License Application to the US Food and Drug Administration (FDA).