June 24, 2022 PAO-06-022--NI-07
After decades of treating antibiotics as a panacea, bacteria and fungi have developed antimicrobial resistance (AMR) and evolved into “superbugs.” This has created a global health emergency responsible for the deaths of at least 700,000 people a year — and the situation is only worsening. The World Health Organization (WHO) predicts that if no action is taken there will be 10 million deaths per year by 2050.1 The repercussions are far-reaching, as the WHO estimates that this could trigger an economic crisis, and that the only way out is the development of a new generation of antimicrobial drugs.
Without antibiotics, even common infections can be serious or life-threatening. However, researchers now know that antibiotic overuse can be damaging to the human microbiome and can contribute to a range of diseases. Needless to say, it’s time to move on from existing antibiotics. Armata Pharmaceuticals hopes to end the global antibiotic resistance crisis by focusing on the development of precisely targeted bacteriophage therapeutics. Operating out of a 35,000-ft2 facility in Southern California, Armata is developing an extensive pipeline of both natural and synthetic phage candidates, including clinical programs for Pseudomonas aeruginosa, Staphylococcus aureus, and other pathogens. The company has also partnered with Merck to develop proprietary synthetic phage candidates for an undisclosed infectious disease agent.
Arcellx creates chimeric antigen receptor T (CAR-T) therapies for the treatment of cancer, including multiple myeloma. However, unlike other CAR-T–based therapies, which have a potentially detrimental effect on the immune system (and may lead to a critical autoimmune disorder), Arcellx aims to engineer synthetic binding scaffolds that are “deimmunized,” thus eliminating the risk of an immune response. These scaffolds, or “D-Domains,” are smaller than the binding domains being used in currently available CAR T therapies, giving them a higher transduction rate and lowering the total number of T cells required to be administered, which improves the drug’s toxicity profile.
Arcellx is currently in an ongoing phase I clinical trial of lead candidate CART-ddBCMA. Of the 19 patients evaluable for efficacy, the overall response rate (ORR) is currently 100%. The duration of response rate (DOR) is also promising, as more than half of patients with relapsed/refractory multiple myeloma have experienced an ongoing response for at least one year following treatment. On the basis of these results, the company was able to raise $124 million for its IPO.
High blood pressure is a highly common condition and is potentially life-threatening, especially for those with uncontrolled hypertension. CinCor, a clinical-stage biopharmaceutical company, is focused on addressing this by creating a treatment for hypertension and other cardio-renal diseases. CIN-107, the company’s lead clinical candidate, directly inhibits aldosterone synthase, the enzyme responsible for the synthesis of aldosterone in the adrenal gland.
Aldosterone synthase is encoded by the CYP11B2 gene, which has a low affinity for 11ß-hydroxylase, the enzyme responsible for cortisol synthesis. In multiple preclinical in vivo studies, CIN-107 significantly lowered aldosterone levels without affecting cortisol levels across a wide range of doses and with no serious adverse events reported. Unlike traditional blood pressure medications, CIN-107 stops production at the source to improve this condition. Though the mechanism of action is unique, the candidate is an oral small molecule drug like others on the market, and therefore won’t pose patient delivery challenges. CIN-107 is currently in phase II clinical trials for hypertension and primary aldosteronism. In addition to these indications, the company has plans for a phase II clinical trial later this year to explore its impact on chronic kidney disease
Erasca has a bold mission — to erase cancer. The company is taking a unique approach to doing so, by shutting down one of cancer’s most commonly mutated signaling cascades, the RAS/MAPK pathway. Erasca’s pipeline comprehensively focuses on this pathway through three therapeutic strategies: targeting key upstream and downstream signaling nodes in the RAS/MAPK pathway, targeting the RAS directly, and finally targeting the escape routes that emerge in response to treatment.
The company has several clinical trials in progress evaluating their therapeutic approach against a range of cancers. Instead of targeting a specific type of cancer, Erasca has determined that the pathway itself is the real path forward. The company is on a mission to deliver new therapies to patients, especially as there are approximately 5.5 million new cancer diagnoses annually driven by RAS/MAPK pathway alterations, and over 90% (approximately 5 million patients) lack treatment options.
Cell and gene therapy companies are positioned to make major waves in drug development, and Caribou is set to be a leader of the pack. The company’s proprietary chRDNA (CRISPR hybrid RNA–DNA) technology enables high specificity and genome-editing to treat cancer. chRDNA stands out among the diverse technologies emerging from CRISPR, as it enables multiple genome edits, including multiplex gene insertions and lower levels of off-target editing, making it significantly more targeted than first-generation CRISPR-Cas9 technology.
Caribou’s pipeline treats cancers through a diversified approach. The company is developing genome-edited off-the-shelf CAR-T cell therapies, derived from healthy donor T cells (as opposed to cells extracted from the patient) to improve antitumor activity. Caribou is also developing CAR-NK (natural killer cell) therapies to treat multiple solid tumor types. The company differentiates NK cells from induced pluripotent stem cells (iPSCs) that are edited to address targeting, trafficking, proliferation, and to overcome the immunosuppressive tumor microenvironment. The technology has been promising so far — Caribou recently announced its lead candidate CB-010 as the first allogeneic CAR-T cell therapy to achieve 100% ORR.
The best way to cure diseases is to prevent them entirely, which is largely possible with efficacious vaccines. Aiming to advance this preventative technology is Blue Water Vaccines, a biopharmaceutical company focused on creating transformative vaccines to be distributed globally. Of particular interest is the company’s universal flu vaccine, which it is developing to provide total protection against all virulent strains of influenza.
Blue Water is also developing a Streptococcus pneumoniae (pneumococcus) vaccine candidate designed to specifically prevent highly infectious middle ear infections, known as acute otitis media (AOM), in children. Additionally, Blue Water Vaccines is working on a nanoparticle versatile virus-like particle (VLP) vaccine platform. Through this work, the company hopes to create vaccines for multiple infectious diseases, including norovirus/rotavirus and malaria.
Adagio Therapeutics is fueled by a mission that is both noble and timely — to engineer an effective, long-term solution for the COVID-19 pandemic. The company’s vision is to discover, develop, and commercialize antibody-based solutions to address the current pandemic and to treat other viral diseases that demonstrate pandemic potential.
Adagio aims to treat COVID-19 through its lead product candidate ADG20, which is a neutralizing antibody that works broadly against all strains of coronavirus. ADG20 can be used for both treatment and prevention of COVID-19 and as either a single or combination agent. This technology is fueling the development of further antibodies to treat respiratory viruses that may mimic the current pandemic.
SomaLogic’s SomaScan proprietary platform is a catch-all — it can be used for discovery, validation, and delivery. The assay provides 7,000 highly reproducible measurements of circulating proteins from a single sample of plasma, serum, or urine (only 55 µl) by using Slow Off-Rate Modified Aptamers (called SOMAmer® reagents).
SOMAmer reagents are synthetic ssDNA sequences with protein-like appendages that tightly bind a specific protein target. These reagents are more consistent than antibodies, which is key for reproducibility. The platform enables even very rare proteins to be detected. A system of robotics makes the process highly scalable, with over 1,000 clinical samples being analyzed daily.
Reprogramming your body may sound like science fiction, but Umoja Biopharma hopes to make it a reality. The company is on a mission to create curative treatments for solid tumors and blood cancers by building an integrated system of cellular immunotherapy platforms that reprogram the immune system in vivo to attack cancer.
The vision is to then integrate its technology platforms into therapeutic regimens. As these treatments are so highly personalized, they will ideally work across patients and tumors, regardless of disease progression. Instead of relying on engineered cellular immunotherapies, Umoja Biopharma wants to enable the patient to create engineered immune cells internally. Umoja Biopharma believes that the personalized nature of these in vivo treatments will eliminate the side effects and lengthy timelines associated with cancer therapies.
The more information that’s available about a cell, the better it can be understood — and the greater the potential for more targeted treatment. Drug discovery and development company Eikon is leveraging superior engineering and high-performance computing to analyze single-molecule protein behavior in living cells. Instead of analyzing a picture or past event, Eikon imagines a future in which live cell imaging of a single protein movement contributes to finding cures.
The company is pioneering a new method of drug discovery based on tracking and measuring the movements of individual proteins in living cells. According to the Eikon, assessing protein dynamics will reveal novel biological mechanisms of action, providing new therapeutic approaches that will address both existing and novel drug targets — and these insights will help to power innovative new therapies.
David is Scientific Editor in Chief of the Pharma’s Almanac content enterprise, responsible for directing and generating industry, scientific and research-based content, including client-owned strategic content, in addition to serving as Scientific Research Director for That's Nice. Before joining That’s Nice, David served as a scientific editor for the multidisciplinary scientific journal Annals of the New York Academy of Sciences. He received a B.A. in Biology from New York University in 1999 and a Ph.D. in Genetics and Development from Columbia University in 2008.