S&S On Biotech

In 1934, Mary Walker, a pioneering Scottish physician, successfully, albeit transiently, treated a myasthenia gravis patient with physostigmine, a traditional remedy for treating poisoning with curare. She had noticed that the signs and symptoms of myasthenia gravis resembled those caused by curare, a preparation of plant alkaloids used to arm poison arrows by some indigenous peoples in Central and South America. Her clinical observations were extraordinarily accurate. At a molecular level, c...

Melanoma has been at the very centre of the cancer immunotherapy revolution over the past decade and a half. The CTLA-4 inhibitor Yervoy (ipilimumab), which gained approval in 2011, was the first agent to demonstrate a survival improvement in a phase 3 trial for metastatic melanoma. It was also the first immune checkpoint inhibitor to gain approval, and it kick-started a whole new era in cancer therapy, based on jamming the cancer’s immunosuppressive signals to enable patients’ T-cells to att...

This is a sobering episode that traces the history of the treatment of brain cancer – principally malignant glioma, since it is the most common diagnosis in a thankfully rare oncology indication – and how, unlike many of the indications we have discussed, the treatment options have been limited. The diagnosis of brain cancer often takes too long, partly because headaches and behavioural changes divert patient referrals to other specialities before patients end up at the door of a neurosurgeon...

Ophthalmology has long been a fruitful area for biotechnology innovation. In highly prevalent conditions associated with ageing, such as age-related macular degeneration, or with chronic disease, such as diabetic macular oedema, vascular endothelial growth factor inhibitors have made important contributions to stabilizing vision over the past two decades. Incremental innovation has steadily improved efficacy while lowering the frequency of injections. And newer targets, such as components of ...

For all the extraordinary progress we have seen in basic biological research and in the development of advanced therapies, allergy is an area that seems to be stuck and badly in need of innovation. For some, an allergy may be little worse than an irritant, but for those with severe allergies to certain foods or insect stings, it may be a matter of life and death. The immunotherapy approaches that are still the basis of many development efforts were originally pioneered by Leonard Noon and Joh...

A couple of years ago, PROTACs were ubiquitous. Start-ups were devising increasingly clever ways of making them, while large pharma companies were queuing up to tap into their expertise and their development programs. Proteolysis-targeting chimeras, to give them their full title, emerged as a clever and versatile way of degrading, with exquisite selectivity, disease-associated proteins that were hard to drug by conventional means. First described over two decades ago, by Kathleen Sakamot...

Over 10% of the world’s population – or 850 million people – are estimated to have kidney disease, and the problem is growing rapidly. The vast majority lives in low-income or low-and-middle-income countries, and, without access to primary healthcare, may be unaware of the problem until it is too late – organ failure and early death follow. Only dialysis and organ transplant can prolong the life of patients with kidney failure, but neither is hugely scalable, particularly in low-resource sett...

Human longevity is a precious thing. Some people receive a tragically short amount of it. Others who have it in abundance want even more of it – and a reasonable chunk of the biopharmaceutical industry has organised itself around the goal of delivering it to them. Age-associated diseases encompass a very broad area of human disease, including cancer, cardiovascular disease, and neurodegenerative disease, among many others. These have, obviously, been mainstream concerns for drug develop...

Therapeutic cancer vaccines have had a long and chequered history. The BCG (Bacillus Calmette-Guérin) vaccine, originally developed to protect against tuberculosis in the 1920s, was adopted back in the 1970s as treatment for bladder cancer. When delivered locally to the organ, it elicits an anti-tumor immune response. Progress in recent decades has been painfully slow, however. Only a clutch of therapeutic cancer vaccines has gained approval, and their performance has been decidedly mixed. Pr...

The flow of money is a constant preoccupation of the biotechnology sector, because without it nothing gets done. So, whether the markets are up or down, and whether investors are buying or selling is important, even if it is secondary to the actual business of biotech, which is the discovery and development of therapies that offer improvements over what is currently available. Investor sentiment in biotech is cyclical, based both on external macroeconomic factors and on the sector’s internal ...

The failure of Relyvrio in a post-approval phase 3 study in amyotrophic lateral sclerosis (ALS) means its days as a commercial drug are probably numbered. It initially gained approval in Canada in June 2022 (where it is, confusingly, known as Albrioza) and secured FDA approval the following September. Both approvals rested on the 24-week phase 2 ‘Centaur’ trial, in which the drug showed modest effects as compared with placebo in slowing patients’ decline in physical functions. Those data were...

A 40% share price drop after an investigational drug hits the primary endpoint of a phase 3 trial is not typical. But that’s what happened to Ironwood Pharmaceuticals when it reported data from a trial of apraglutide in patients with intestinal failure due to short bowel syndrome (SBS-IF). The condition arises from the loss of gut function following surgical removal of a large portion of the small intestine due to conditions such as severe inflammatory bowel disease or cancer in adults o...

By late June or early July we’ll know whether Alnylam’s decision to alter the design of its phase 3 ‘Healios B’ study of Amvuttra (vutrisiran) in transthyretin amyloidosis with cardiomyopathy (ATTR-CM) was a good one. The short-interfering RNA (siRNA) drug is already approved in ATTR with polyneuropathy (ATTR-PN), a debilitating, fatal condition in which misfolded transthyretin proteins clump together and create damaging deposits in the peripheral nerves. But about ten times as many pati...

Novartis’s recent €2.7 billion ($2.9 billion) offer for Morphosys is the very stuff of biotechnology. The medium-sized deal adds two clinical-stage cancer drug candidates to its pipeline. Both operate through epigenetic mechanisms – they aim to alter dysfunctional gene expression programs and thereby interfere with the signals that maintain cancer growth. Pelabresib, a potential first-in-class inhibitor of bromodomain and extra-terminal motif (BET) proteins, has completed a phase 3 trial...

Hereditary angioedema (HAE), arguably, represents an ideal case of the Orphan Drug rules in action. Because of the incentives on offer, a mini-cluster of firms has, over the past fifteen years, developed a well-stocked cabinet of therapies for this rare disease. The condition is linked to deficiencies in C1 esterase inhibitor activity and results in dysregulation of the kinin-kallikrein pathway, which is involved in regulating inflammation, blood pressure, and coagulation. The ultimate c...

Non-alcoholic steatohepatitis (NASH) and its precursor non-alcoholic fatty liver disease (NAFLD) have recently been redesignated as MASH and MASLD – metabolic dysfunction-associated steatohepatitis and metabolic dysfunction-associated steatotic liver disease, respectively. What hasn’t changed is the sheer difficulty of establishing clinical efficacy in these indications. They have long been known as a ‘silent killer’, owing to the asymptomatic nature of the pathology. And yet, the gradual acc...

Sanofi’s partial acquisition of Inhibrx recalls earlier transactions, such as Pfizer’s acquisition of BioHaven or, to go back even further, Johnson & Johnson’s acquisition of Actelion, in which assets deemed surplus to the acquirer’s needs were spun out into new entities. In the case of Inhibrx, Sanofi wanted just one programme, INBRX-101, its investigational drug for alpha1-anti-trypsin deficiency (AATD), a genetic condition arising from a point mutation in the SERPINA1 gene, which encod...

The use of radiation in medicine began with the work of the great pioneers Marie Curie, her husband Pierre, and Henri Becquerel. In the 1940s, Samuel Hertz, Samuel Seidlin, and William Beierwaltes established radioactive iodine (I-131) as a treatment for overactive thyroid and thyroid cancer. The effects of radiation are not cell-specific – it is inherently damaging to all cells, so the focus of current development efforts is on delivering a targeted dose of radiation, by attaching a rad...

The annual JP Morgan Healthcare Conference, held in San Francisco every January, marks the start of the biotech industry’s new year. It’s the time when biotechnology companies of all shapes and sizes set out their stall for the year ahead, hoping to attract the attention – and the dollars – of big pharma. It’s the ideal time to take the temperature of the industry. And right now, it appears to be emerging from the big chill of 2023. The Nasdaq Biotechnology Index continues the climb it b...

In its own words, the U.S. Federal Trade Commission’s opposition to a licensing deal between Sanofi and the biotechnology firm Maze Therapeutics, “is a case about a monopolist seeking to eliminate a nascent threat to its monopoly”. Cue howls of complaint by VC’s and public market investors that government scrutiny is preventing innovation. True enough, acquisitions, mergers and licensing transactions between biotech companies and bigger biotech or pharma companies are the lifeblood of t...

Have antibody-drug conjugates peaked—or is there more innovation to come?Antibody-drug conjugates (ADCs) are complex products, and it has taken the field some time to iron out some of the difficulties that hampered their initial development. The basic idea is simple—by attaching a cytotoxic payload to an antibody that targets a protein expressed (ideally uniquely) on the surface of cancer cells, you can combine the exquisite specificity of antibody-based therapies with the potency of che...

The UK approval of the CRISPR-Cas9 gene editing therapy Casgevy (exagamglogene autotemcel or ‘exa-cel’) for treating the inherited blood disorders sickle cell disease (SCD) or transfusion-dependent b-thalassemia is an historic scientific and clinical milestone. Coming barely more than a decade after the technology was invented, it represents a major achievement for its developers Crispr Therapeutics and Vertex Pharmaceuticals. But this particular approval is largely of academic interest, as v...

When they first emerged, chimeric antigen receptor T-cell (CAR-T) therapies seemed like the stuff of science fiction. The basic idea of reprogramming T-cells is decades old. It involves isolating a patient’s T-cells, genetically modifying them to express a new receptor that recognizes a target protein, such as an antigen expressed by a cancer cell, and putting them back into the body, where they can expand and attack cancer cells. In early clinical trials, they had dramatic, curative eff...

When I was a global product manager in big pharma, my US counterpart mentioned to me one day that “we do generics properly in the US, not like you do in Europe.” He meant that when a small molecule went generic in the US, and the 180-day first-to-file exclusivity expired, the former branded price was massacred. It was true, in the first year SmithKline’s Tagamet went generic, they lost 80% of sales. Why then does the same not happen for biosimilars, which are meant to be the generic equivalen...

When I was a global product manager in big pharma, my US counterpart mentioned to me one day that “we do generics properly in the US, not like you do in Europe.” He meant that when a small molecule went generic in the US, and the 180-day first-to-file exclusivity expired, the former branded price was massacred. It was true, in the first year SmithKline’s Tagamet went generic, they lost 80% of sales. Why then does the same not happen for biosimilars which are meant to be the generic equivalent...

Has gene therapy delivered on its promise? Or is that promise still to be realised? What are the main problems that limit the safety and efficacy of those gene therapies that have gained approval or are about to do so? And how can the experience the field has gained so far be harnessed to the development of better approaches?Send us a text Suggestion box (Suggestions on future episodes, points for clarification, comments, etc.) Subscribe (Get notified when new episodes are available. NO mark...

Although the Covid-19 pandemic may not be over, it appears to have entered its concluding phase. Sales of Covid-19 vaccines, as well as therapies, are falling sharply, as are the share prices of their producers. But what are we left with? And what other opportunities are open to the mRNA vaccine technology that performed so powerfully during the pandemic? And how can it be improved? Send us a text Suggestion box (Suggestions on future episodes, points for clarification, comments, et...

With nearly three million infections involving antimicrobial resistant bacteria in the US each year and more than 35,000 deaths, you would have thought that the development of new agents to treat antimicrobial resistant infections would be a priority for both governments and biotech companies. But for a number of reasons, it isn’t. Send us a text Suggestion box (Suggestions on future episodes, points for clarification, comments, etc.) Subscribe (Get notified when new episodes are availa...

Skinny jabs. Are they hype, or hope?Send us a text Suggestion box (Suggestions on future episodes, points for clarification, comments, etc.) Subscribe (Get notified when new episodes are available. NO marketing!) Follow us on LinkedIn Disclaimer

In the seasonal sequence of biotech fundraising, we are about to enter the ‘back to school’ season where biotech companies that are in need of funding, start their roadshows with institutional investors to gain those funds. Send us a text Suggestion box (Suggestions on future episodes, points for clarification, comments, etc.) Subscribe (Get notified when new episodes are available. NO marketing!) Follow us on LinkedIn Disclaimer