At the start of 2023, the website for Pfizer CenterOne posted an article titled, “What Trends Will Shape the Pharma and Biotech Industries in 2023?” It quoted Rick L. Knight, the company’s global head of strategic account management, as follows: “We can continue to expect to see innovative products emerge from the development pipeline, but we will also be challenged to adapt to the changing needs of our partners, as many companies are likely to face tighter constraints on investment, resources, and timelines.”

In other words, participating in the biopharma business means striking a balance between confidence and cautiousness. Both of these qualities played into the past year’s business stories—as did the power of people to shape events, from patients willing to take promising new treatments in clinical trials, to activist investors intent on jumpstarting underperforming stocks. The top 10 stories are revisited here. All were covered by GEN in 2023.

AI: Applications in drug discovery

Years of curiosity and hype about artificial intelligence (AI) gave way to significant progress. Nvidia’s stock price rose from $148.59 on January 3 to $494.27 on November 14. The surge was unimpeded by a police raid on the company’s French offices. Recursion Pharmaceuticals also saw its stock soar after reaping a $50 million investment from Nvidia. In February, the FDA granted its first-ever orphan drug designation to Insilico Medicine for its idiopathic pulmonary fibrosis candidate INS018_055. INS018_055 dosed its first Phase II patient in June and later partnered with Exelixis to develop ISM3091 for BRCA-mutant tumors.

Zhavoronkov, PhD, and Feng Ren, PhD
Insilico Medicine supports its development programs through an AI-driven robotics laboratory in Suzhou, China. Shown here [L–R] in the lab are Alex Zhavoronkov, PhD, and Feng Ren, PhD. Zhavoronkov is Insilico’s founder and co-CEO. Ren is Insilico’s co-CEO, CSO, and head of R&D.

Alzheimer’s: Finally, some hope

Alzheimer’s disease is notoriously tough to target via new drugs. A 2014 Cleveland Clinic study found a 99.6% failure rate. But Eisai and Biogen found success—without the controversy or history making of their previous Alzheimer’s drug, Aduhelm (aducanumab-avwa)—when their Leqembi (lecanumab-irmb) scored an FDA emergency use authorization in January. Full approval came six months later. As 2023 ended, Eli Lilly and Company awaited an FDA decision on its Alzheimer’s drug donanemab, while smaller companies, including Cognition Therapeutics, saw clinical successes, giving patients some long-awaited hope. All that activity is expected to drive industry growth, with Morningstar projecting 2027 sales of $4 billion for Leqembi and $4.877 billion for donanemab.

Base editing: Positive proof of concept

The first base editing therapy to reach the clinic dazzled researchers in December by generating positive first-in-human proof-of-concept data. At the American Heart Association Scientific Sessions 2023, Verve Therapeutics announced data from its Phase Ib heart-1 trial (NCT05398029) showing that one month after treatment with VERVE-101, heterozygous familial hypercholesterolemia patients showed dose-dependent reductions in low-density lipoprotein cholesterol and in pharmacodynamic measures of blood PCSK9 protein levels. “Can we precisely rewrite the genetic code—make a single DNA spelling change—in the liver of a human being for clinical effect? Yes!” exclaimed Sekar Kathiresan, MD, Verve’s co-founder and CEO.

Andrew Bellinger, MD, PhD
Verve Therapeutics’ CSO, Andrew Bellinger, MD, PhD, presents the first human proof-of-concept data for VERVE-101, the first base editing therapy to reach the clinic. The occasion was the American Heart Association’s Scientific Sessions 2023, a meeting that was held November 11–13 in Philadelphia, PA. [Kiran Musunuru, MD, PhD]

Cell and gene therapies: Growth and milestones

Cell and gene therapy development continued steadily, with 65 nongenetically modified cell therapies, 27 gene therapies, and 26 RNA therapies approved worldwide at the end of Q3 2023 (up from 59, 22, and 21, respectively, a year earlier), according to a report from the American Society of Gene and Cell Therapy. For gene therapy, June was a historic month as the FDA approved both Sarepta Therapeutics’ Elevidys (delandistrogene moxeparvovec-rokl, formerly SRP-9001), the first gene therapy indicated for a form of Duchenne muscular dystrophy, as well as BioMarin Pharmaceutical’s Roctavian (valoctocogene roxaparvovec-rvox), the first gene therapy to be authorized for severe hemophilia A.

Clusters: Bay Area back on top … for now

The San Francisco Bay Area returned to the top of GEN’s annual Top 10 U.S. Biopharma Clusters A-List, edging out longtime leader Boston/Cambridge, MA, by raising more venture capital during 2022—likely reflecting last year’s post-pandemic bear market since Boston/Cambridge topped the Bay Area in venture capital between January and June. The Bay Area is struggling to retain jobs and employers given the industry-wide slowdown and San Francisco’s downtown crime and homelessness, which has driven away banks and retailers. Following complaints of hotel price gouging, J.P. Morgan committed to hosting its annual Healthcare Conference in San Francisco only through 2024, amid speculation about a move to Florida in 2025.

CRISPR: Clinical and regulatory progress

Victoria Gray
Victoria Gray

Vertex Pharmaceuticals and CRISPR Therapeutics brought the first CRISPR-Cas9 gene edited therapy, a severe sickle-cell disease candidate called exagamglogene autotemcel (exa-cel), through successful pivotal studies to an FDA decision evaluation. (At the time of writing, a decision was expected on December 8.) At a day-long hearing, an FDA advisory committee set the stage for the historic decision by centering its review on off-target effects, apparently satisfied with exa-cel’s safety and efficacy: The therapy has been shown durable in the first treated patient, Victoria Gray, for four years. In addition to sickle-cell disease, exa-cel is also being developed for transfusion-dependent beta-thalassemia, with an FDA decision expected on March 30, 2024.

Deals: M&A bounces back, but VC slumps

Merger and acquisition (M&A) deals bounced back in 2023, paced by Pfizer’s planned $43 billion acquisition of Seagen, then Merck & Co.’s $10.8 billion buyout of Prometheus Biosciences. Amgen’s $27.8 billion purchase of Horizon Therapeutics, announced in December 2022, closed in October after the U.S. Federal Trade Commission backtracked on its earlier threat to torpedo the deal. However, biopharma venture capital activity slumped during the first three quarters of 2023, declining 31% year-over-year in dollar value ($16.3 billion vs. $23.6 billion in Q1–Q3 2022) but falling only 14% year-over-year in number of deals (707 vs. 821), according to quarterly Venture Monitor reports by PitchBook and the National Venture Capital Association.

Carl C. Icahn
Carl C. Icahn

Illumina: Icahn compels changes

Carl C. Icahn cited Illumina’s $50 billion drop in market capitalization, weak recent quarterly results, and $7.1 billion purchase, over regulators’ objections, of cancer blood test developer Grail as reasons for his spring proxy battle against the company’s board and then-CEO Francis deSouza. (These concerns were explored in an exclusive interview on GEN’sClose to the Edge.”) Shareholders ousted a deSouza ally as chairman and elected an Icahn nominee to the board, leading to deSouza’s resignation. Icahn rekindled his battle against deSouza and board allies in October by suing them in Delaware Chancery Court, alleging that they breached their fiduciary duty to shareholders of the sequencing giant. The case is expected to run well into 2024 if not beyond.

IPOs: Still sluggish despite recent offerings

David R. Liu, PhD
David R. Liu, PhD

The initial public offering (IPO) market showed signs of life in the second half of 2023, with 11 companies joining the 8 that issued their first public shares in the first half. But markets have remained sluggish, if not bearish, and the fact that share prices of most IPO companies have fallen from their first trading days have kept many more companies on the sidelines, pursuing additional private financing. Acelyrin scored the biggest IPO through November 14, raising $621 million gross proceeds ($573.7 million in net proceeds) in May. Apogee Therapeutics followed in July with $345.1 million gross ($315.4 million net).

Prime editing: New options

U.S. Patent No. 11,572,556, granted in February and assigned to MIT, covers a genome editing tool called PASTE (programmable addition via site-specific targeting elements). PASTE combines elements of CRISPR and prime editing with a pair of enzymes designed to enable the integration of large segments of DNA without incurring double-stranded DNA breaks.

Jacob S. Sherkow, JD
Jacob S. Sherkow, JD

Prime Medicine, which licenses prime editing technology developed in the lab of David R. Liu, PhD, and which uses a prime editing platform called PASSIGE (prime-assisted site-specific integrase gene editing), expressed confidence in its patent portfolio. Liu and Prime expect prime editing’s first clinical trial in 2024.

Jacob S. Sherkow, JD, an authority on the long-standing CRISPR-Cas9 patent standoff, told GEN Edge that MIT and PASTE’s inventors can likely show their technology is novel and useful. He added, however, that nonobviousness may be deemed less clear should the PASTE patent be challenged.

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