Drug Discovery and Development
Next up in the biopharmaceutical R&D pipeline
From life-threatening illnesses to orphan, rare and chronic diseases, thousands of patients live with the hope that the life sciences industry will bring new medicines that will raise their standard of health, or even save their lives. A record-breaking 8,000 medicines currently in development, 74% of which are first-in-class, is a sign of hope. Among the most remarkable advances in recent years are harnessing the body’s immune system to fight cancer through immune-oncology, tackling rare genetic disorders, a return to CNS focuses, and a range of CAR-T cell therapies driving unprecedented remission rates for cancer patients, and these will remain the therapeutic areas under the spotlight in 2023.
Immuno-therapy and harnessing the power of the cell
Cell and gene therapies (CGT) remain among the fastest-growing areas of therapeutics in the US. With genomic medicine poised to drive drug development in the coming decades, several US firms are pioneering technology platforms in allogeneic cell therapy for oncology and in vivo gene therapy to address monogenetic diseases. Recent years have witnessed a significant uptick in cell and gene growth, with interest going beyond biotechs engineering CAR-T cell therapies; Biocom California recently established a Cell and Gene Therapy Committee.
Several factors are behind the forecast growth of the CGT market to US$10 billion by 2026: an uptick in clinical trials, more government funding for cancer research, and growing regulatory acceptance of CGT, with five therapies approved by the FDA in 2022 (Q4 2022 saw two gene therapies approved in the US, Hemgenix for hemophilia B, and Adstiladrin for bladder cancer). The FDA forecasts that by 2025, it will approve between 10-20 therapies annually. Regulators even created a “Super Office” in a push to shorten these drugs’ time for approval. And a sneak peek at the pipeline of products in Phase 3 clinical trials suggests the number of approvals is likely to rise acutely in the coming months: 52 C&G (cell and gene) launches are expected in 2024, according to the FDA.
The industry is at a critical inflection point in the commercialization of CGT. California-based Sangamo Therapeutics is currently developing a Hemophilia A program with Pfizer and a clinical trial-stage CAR-Treg cell therapy for renal transplant. The firm has its finger on a novel technology that could revolutionize gene editing: Zinc finger (ZF) technology. Building on a pipeline of three late-stage assets – those that have investors’ favor in these uncertain times – CEO Sandy Macrae explained: “Our proprietary zinc finger technology allows us to power a complete suite of genomic medicine capabilities, providing a unique approach to gene therapy, cell therapy, and gene editing.”
Few technologies in the life sciences industry hold as much promise as CGT. This technology can target the underlying cause of a disease with curative potential. Daniel Palmacci heads the C&G division at Lonza, one of the world’s largest CDMOs, and is bullish on the future of the field, with close to 3,726 products in development across the industry according to the American Society of Gene & Cell Therapy. He shared: “CGT presents perhaps the biggest hope in life sciences, as it can treat many indications such as cancer and genetic disorders effectively – and in some cases even have the potential to be curative.”
When asked about the trends likely to shape the biopharmaceutical industry in 2023, Tyrone Brewer, president of US oncology at Janssen, was categoric: immuno-oncology will remain a key topic prompting further drug discovery. Leveraging the patient’s immune system is a key capability to add to biopharma’s core competencies, and Janssen appears to be pioneering that area. Brewer detailed that approach: “This focus is so essential to Janssen that we formed a dedicated multi-functional team entirely focused on immunotherapy research. This is a key area of development and innovation for Janssen and across oncology in the coming years.”
As oncology and rare diseases remain the most targeted indications by gene therapies, the oncology area will likely continue to lead industry demand in the near term. “Oncology constitutes approximately 40% of dollars spent on R&D in the industry. This was thus a key focus area for us and one of our earlier acquisitions was SMS-Oncology, a Dutch oncology-focused CRO”, explained Mark Goldberg, CEO of Allucent, a CRO supporting small and mid-sized biopharma firms.
Finally, mRNA has most lucratively been applied in Covid-19 vaccines, but as this pandemic page closes, mRNA therapeutics still hold promises to unlock other unmet medical needs. Before lawsuits play out between Pfizer/BioNTech and Moderna to settle disputes over mRNA vaccine patents, the RNA pipeline noticeably grew the most among other therapeutic areas throughout 2022, increasing by 17%. Manufacturers are closely watching those developments. Evonik’s US$220 million investment in partnership with the government to develop new mRNA therapies is a testimony that the area remains relevant post-pandemic, as outlined by Paul Spencer, head of drug delivery and product at Evonik Health Care: “The investments we are making in North America to better improve the delivery of drugs are crucial. We believe mRNA therapeutics are transformative.”
Next-generation therapies are poised to make a comeback in 2023. According to the Alliance for Regenerative Medicine, in 2022, developers of cell therapies, cell-based immune-oncology therapies, gene therapies, and tissue engineering therapies raised a total of US$6.4 billion and oversaw 2,093 active trials during the first half of 2022—less than half the US$14.1 billion of H1 2021. Today, about 20 gene therapies and 10 CAR-T treatments are pending approval in 2023, and more specialty therapies are on the horizon. Since the past year, the FDA has received more than 3,000 Investigational New Drug (IND) applications to study CGT in clinical trials.
Neurology candidates face setbacks, but CNS is back
Like in 2022, Alzheimer's drugs topped the list of Evaluate Vantage’s most anticipated releases of 2023. Big pharma and ambitious biotechs tackling neurodegenerative diseases have experienced ups and downs in recent years. In November 2022, Roche’s gantenerumab failed to meet the primary endpoint in Phase 3 clinical studies, adding to turmoil and uncertainty among firms with Alzheimer ambitions. In early 2023, the FDA did not grant accelerated approval to Eli Lilly’s Alzheimer’s candidate, donanemab. The Phase 3 trial topline data read-out expected later in 2023 will be crucial for this therapeutic field. On the other hand, Eisai and Biogen’s lecanemab unveiled a surprise win in a Phase 3 study, and in January 2023, lecanemab received FDA approval, with the candidate forecasted to amount to US$3 billion in sales by 2028.
Targeting brain receptors is incredibly complex, and with most biotechs experiencing clinical trial failures – such as Aptinyx’s NYX-458 to treat Parkinson’s – coupled with harsh economic conditions, some CNS firms have shifted their focus towards new therapeutic areas. Aphios develops CNS therapeutics and decided in 2022 to make a strategic shift towards Alzheimer’s disease following lecanemab’s approval. President and CEO Trevor P. Castor detailed his company’s approach: “Instead of focusing on one cause, beta-amyloid plaques, we are looking at all the causes of Alzheimer's disease including beta-amyloid, tau entanglement, enzymatic changes but particularly inflammation in the brain. We are exploring how to address brain inflammation and how our genetic makeup changes as we age promoting more inflammation in the CNS.”
“A reemerging area today is central nervous system (CNS) diseases. For a while, this area was out of favor in the investment community due to many failures. Recently we have started to see some successes which give hope to populations with CNS. Another modality receiving attention is cell and gene therapy.”
Mark A. Goldberg, CEO, Allucent
The severe unmet needs in the CNS space, coupled with a declining mental health picture post-pandemic in the US, make the need to leverage new technologies for breakthroughs ever more pressing. Emer Leahy, president, and CEO of PsychoGenics, noticed an increased interest in the firm’s Cube Technology. In collaboration with Synovion, PsychoGenics is developing ulotaront, a TAAR1 antipsychotic for the treatment of schizophrenia and Parkinson's, which has the potential to be the first AI-discovered novel drug to be marketed. Leahy also pointed to a growing interest in psychiatric disorders and more receptiveness to phenotypic drug discovery. In her opinion: “The target-based approach to drug discovery has not been very successful in CNS in general, largely due to the complexity of the poorly defined conditions with multiple susceptibility genes, epigenetics, and the environment playing a role.”
There is no doubt that CNS is back on investors’ minds. Yet, industry leaders remain lucid regarding the necessary efforts to achieve fundamental knowledge of CNS diseases. More research, failures, and studies will be needed before breakthroughs revolutionize the lives of patients with neurodegenerative disorders. But the industry is committed to providing these patients with hope.
Article header image courtesy of Pace® Life Sciences