【Editor’s note】FYI, this article has 21175 words in total

On August 5, 2024, industry media Fierce Biotech released the Fierce 15 list.

This list was first published in 2003 and has since announced more than three hundred companies, some of which have entered the list multiple times, and some years have included more than 15 companies.

Currently, among these three hundred companies, some have been acquired, some have gone public, and others have gone out of business.

Although the fate of the selected companies varies, it is undeniable that the Fierce 15 list has indeed successfully identified many star Biotech companies such as Ambrx, AC Immune, and EQRX.

For many investors, the Fierce 15 list has undoubtedly become one of the key reference directions for them to understand the latest trends in the pharmaceutical industry and technology hotspots.

According to Fierce Biotech’s disclosure, each company on the list is chosen from a hundred, not only do they need to have real technological innovation, but they also need to meet many conditions such as good partnership relationships, venture capital, and market competitive position.

So, for startup Biotech companies, being selected for the Fierce 15 list is an honor and a recognition of their technological innovation, business model, and market potential.

Indeed, this year’s selected Biotech companies have all proudly “displayed” this honor on their official websites.

Below, Drug Times will analyze each of the 15 Biotech companies selected this year, to see exactly where their “strength” lies.

01

Abdera Therapeutics

Abdera Therapeutics was established in 2020, focusing on radioisotope technology for oncology treatment.

Fierce Biotech believes that with the impressive sales growth of Novartis’s nuclear drugs Pluvicto and Lutathera, the potential of the nuclear medicine track in the future is enormous. However, the global research targets for nuclear medicine are relatively concentrated: SSTR and PSMA.

Abdera’s core technology platform, ROVEr™, can screen for a new generation of nuclear medicine targets, rather than being limited to existing small ligands or large proteins.

Currently, ABD-147, developed based on the ROVEr™ platform, is the first new generation of nuclear medicine targeting DLL3 with the radioisotope 225Ac.

In June of this year, the FDA approved the IND for this drug, and Abdera plans to start Phase 1 clinical trials in the second half of this year.

In addition, Abdera has a good ability to enter the market with funding. In 2023, while coming out of stealth mode, the company announced that it had raised $142 million in Series A and Series B financing rounds.

02

Ascidian Therapeutics

Ascidian Therapeutics was also established in 2020, focusing on RNA therapy for ophthalmology and CNS diseases.

Fierce Biotech believes that the company has a good corporate culture, and the team of about 50 people is quite cohesive. Of course, the most core aspect is its pioneering RNA exon editing technology platform.

This platform combines advanced computational biology with high-throughput molecular biology screening. Compared with existing CRISPR and base editing technologies, it can not only target large genes and highly variable bases but also maintain the natural gene expression patterns and levels, supporting the editing of RNA exons on a scale of thousands of bases.

The significance is that this gene editing technology is expected to further reduce the risk of off-target effects and the occurrence of related adverse reactions.

In June 2024, the technology successfully attracted Roche, and the two parties reached a cooperation agreement. Ascidian will use its RNA exon editing platform to screen CNS targets for Roche.

The total value of the deal is $1.8 billion, with an upfront payment of $42 million.

Currently, the company’s most advanced project is the research therapy ACDN-01 for ABCA4 retinal degeneration, which is about to enter Phase 1 clinical trials.

03

BigHat Biosciences

BigHat Biosciences was founded in 2019, and unlike the previous two companies, it is an AI company, which means it uses artificial intelligence to help design and develop protein antibodies.

Since 2014, with major pharmaceutical companies competing to enter the anti-PD1/PD-L1 antibody immunotherapy field, various new drug forms such as bispecific antibodies, multispecific antibodies, and ADCs have emerged.

Many disease treatment methods have made substantial leaps, but the structure of effective antibodies for target proteins is too complex. Designing and screening effective antibodies takes a lot of time, and the biggest challenge is determining the sequence and structure of the antibody proteins.

The Milliner™ antibody design platform launched by BigHat targets this pain point. The platform not only integrates artificial intelligence algorithms but is also directly connected to the operating laboratory, capable of completing projects in a few days that used to take several weeks.

Based on this, BigHat has successively reached cooperation with several MNCs such as Amgen, Merck, and AbbVie to jointly develop the next generation of antibody and protein therapies.

In terms of financing, from 2021 to 2022, BigHat obtained a total of $94 million in Series A and Series B financing, with investors including Amgen and BMS.

04

Cour Pharmaceuticals

Cour Pharmaceuticals was established in 2013, focusing on its reverse vaccine technology for the treatment of autoimmune diseases.

Traditionally, vaccines stimulate the immune system to produce memory by introducing a part of the pathogen/weakened/inactivated pathogen, so that it can respond quickly when encountering the real pathogen. The “reverse vaccine,” on the other hand, is trying to remove or weaken the immune system’s memory response to certain antigens.

Cour uses nanoparticles to specifically bind to antigens that cause the immune system to attack self-tissues, simply put: “deceive” the immune system’s memory of specific antigens.

Currently, the company has seven research pipelines, among which the faster progress is CNP-101 (TAK-101) in cooperation with Takeda, which is currently in the phase II clinical trial for celiac disease.

Another drug is CNP-104, in cooperation with Ironwood Pharmaceuticals, which is currently in the phase II clinical trial for primary biliary cholangitis.

In addition, its research therapy for myasthenia gravis, CNP-106, has obtained clinical proof of concept, and its phase 2a clinical trial is recruiting patients.

At the beginning of this year, the company completed a Series A financing of $105 million, with investors including Roche, Pfizer, Bristol-Myers Squibb, and other MNCs.

05

Excision BioTherapeutics

Excision BioTherapeutics was founded in 2015 and restructured in 2019, focusing on CRISPR technology for the treatment of viral infections.

One of the highlights of Excision is its Nobel Prize background; its technology platform comes from the Nobel Prize-winning laboratories, licensed from the Jennifer Doudna laboratory at the University of California, Berkeley, and the Khalili laboratory at Temple University.

In 2019, the Excision team achieved a major scientific milestone when its technology removed HIV DNA from the genome of living mice.

Excision’s core pipeline, EBT-101, is developed based on this scientific success and is used to treat HIV. Therefore, EBT-101 is also the world’s first in vivo gene editing therapy for HIV infection based on CRISPR technology.

Unfortunately, in May of this year, Excision announced that EBT-101 failed in early research.

The results of the first phase of the trial on five patients showed that EBT-101 could not effectively suppress the HIV virus. It was reported that three patients quickly experienced a rebound of the virus after stopping antiretroviral therapy and needed to resume conventional treatment.

However, in addition to the lead pipeline EBT-101 for treating HIV infection, the company also has three other pipelines: EBT-103 for treating human polyomavirus infection, EBT-104 for treating herpes simplex virus infection, and EBT-107 for treating hepatitis B virus infection.

In 2021, Excision raised $60 million through Series A financing. In an interview with Fierce Biotech, the company’s CEO stated that they would raise Series B financing as soon as possible.

06

Fauna Bio

Fauna Bio was founded in 2018. Although it is an AI company like BigHat Biosciences, its R&D approach is quite different.

Fauna’s approach is very innovative. The company’s Convergence™ AI platform analyzes data collected from the protective adaptations of hibernation biology (and other extreme adaptations) to identify drug targets for humans.

In simple terms, it draws inspiration from nature.

It first studies the hibernation biology of hibernating animals (such as ground squirrels) or the genetic sequences of other mammals in extreme environments like drought.

Then, using Convergence™, it constructs a biomedical knowledge map by combining human patient data with data from animals that can naturally resist diseases. It is further trained to select drug targets.

Currently, Fauna Bio has collected thousands of transcriptomes, proteomes, and epigenetic profiles.

In December 2023, such an innovative research direction was discovered by Eli Lilly, and the two parties reached a cooperation worth nearly $500 million, that is, to use the Convergence™ AI platform to support preclinical drug discovery for obesity.

In an interview with Fierce Biotech, Fauna’s CEO said, “The changes in tau seen in early Alzheimer’s disease occur in some animals every few weeks, but they clear it every time they come out of hibernation.”

In addition, she listed acute kidney injury, fibrosis, heart disease, and other CNS disease targets, all of which can be discovered through their AI platform.

07

Gilgamesh Pharmaceuticals

Gilgamesh Pharmaceuticals was established in 2019, and it is a company spun out from the neurochemistry laboratory of Dalibor Sames at Columbia University.

The company is committed to exploring a class of non-hallucinogenic psychedelic compounds for the treatment of mental illnesses.

Medications based on hallucinogens can reconnect brain cells without causing hallucinations. That is, they use psychedelics to stimulate the growth of new branches called dendritic trees and dendritic branches on neurons, thereby having a lasting impact on the brain.

These new branches can make contact with adjacent neurons, forming a complex network of interconnected brain cells. The rewiring of this neural circuitry helps to improve mood, combat depression, and increase overall well-being.

Gilgamesh’s goal is to develop drugs with similar therapeutic effects but without hallucinogenic side effects.

Currently, Gilgamesh has two candidate drugs in Phase II clinical trials. One is the 5-HT2a receptor agonist GM-2505, used for the treatment of severe and treatment-resistant depression.

The other is the NMDA receptor agonist GM-1020, also used for the treatment of severe depression, with the advantage of being usable at home.

Nowadays, as hallucinogens such as psilocybin, ketamine, and MDMA are increasingly close to obtaining regulatory approval, the field of neuroplasticity drug development is also heating up.

In May of this year, Gilgamesh reached a cooperation with AbbVie to jointly develop a new generation of mental illness therapies based on hallucinogens.

Gilgamesh received an upfront payment of $65 million, with the total transaction value reaching as high as $2.015 billion.

08

iECURE

iECURE was established in 2021, focusing on gene-editing technology for the treatment of specific genetic diseases.

The co-founder of iECURE is Professor James Wilson, a pioneer in the field of gene therapy, from whose laboratory iECURE has licensed 13 pipelines.

Several of these pipelines utilize gene insertion and replacement methods to replace defective genes with healthy ones, performing gene editing work within the patient’s body.

This means that its therapies have the potential to resolve hundreds of mutations in one go.

In March 2023, the company’s core pipeline, GTP-506, a gene therapy using dual-vector AAV delivery, was granted orphan drug designation by the European Commission for the treatment of Ornithine Transcarbamylase (OTC) deficiency.

Previously, GTP-506 had already received orphan drug designation and pediatric rare disease qualification from the FDA in this disease area.

Since its establishment, iECURE has raised a total of more than $115 million. The company’s CEO hinted in an interview with Fierce Biotech that the next round of financing is imminent.

09

ILiAD Biotechnologies

ILiAD Biotechnologies is the oldest “age” company on this list. The company was founded in 2012 and is also quite “old-fashioned” in its research field – pertussis vaccine.

In recent years, the incidence of pertussis has been increasing worldwide. According to data from ILiAD, pertussis causes about 16 million infections and approximately 200,000 child deaths each year.

Traditional pertussis vaccines, whether whole-cell pertussis vaccines or acellular pertussis vaccines, both have the problem of insufficient immune durability.

Although optimizing vaccination strategies (such as regular booster immunizations) has a certain effect on the entire population’s resistance to pertussis, the problem of rapidly weakening immunity after vaccination cannot be completely avoided.

The CEO of ILiAD said in an interview with Fierce Biotech, “There are more than 7 billion people on Earth, but not a single person has proper immunity against Bordetella pertussis.”

The most advanced new vaccine in development, an attenuated live pertussis vaccine, is ILiAD’s BPZE1. It can cause a highly protective immune response against Bordetella pertussis infection with just a single nasal administration.

Recently published phase 2b clinical trial results show that BPZE1 stimulates secretory immunoglobulin A against Bordetella pertussis in adolescents aged 6-17. Currently, the drug has achieved positive results in 6 clinical trials.

In September 2022, ILiAD completed a Series D financing of $42.8 million to advance the clinical progress of BPZE1.

10

Kimer Med

Kimer Med was established in 2020, and in the opinion of this author, the company’s research and development field is overly “ahead of its time.”

The company intends to develop a universal target that can address almost all viruses.

In 2011, when Dr. Todd Rider announced his groundbreaking discovery of DRACO, it captured the world’s attention. The discovery was called “visionary” by the White House and was named one of the best inventions of the year by Time magazine.

DRACO can be simply understood as a protein with three functions.

The first function is to enter the cell wall under normal conditions, the second function is to bind to long fragments of double-stranded RNA (dsRNA) produced by the virus, and the third function is to induce cell apoptosis.

Although it sounds good, Dr. Todd Rider did not secure funding. Kimer Med was founded in March 2020, during the peak of the COVID-19 pandemic.

Kimer Med wanted to draw inspiration for COVID-19 treatment from DRACO, but due to the omission of key information in DRACO papers and related patents, the company spent two years and millions of dollars to announce Rider’s achievements and fill in the gaps.

Now, DRACO has been renamed VTose. According to Kimer Med, the antiviral activity of this treatment pattern has been observed in more than 15 types of human viruses, including viruses for which there are currently no approved therapies, such as dengue virus and Zika virus.

Currently, the company is in the process of Series A financing, planning to raise $14 million to support the main research therapy for dengue virus into human clinical trials.

It is worth mentioning that Kimer Med stated that the therapy has shown 100% efficacy against four types of dengue virus in vitro experiments.

11

NodThera

NodThera was established in 2016, focusing on the development of NLRP3 inflammasome inhibitors for the treatment of various inflammatory diseases.

The NLRP3 inflammasome is a highly validated target for anti-inflammatory drugs, acting as a key regulator of the innate immune response, capable of recognizing a variety of pathogenic microorganisms and stress-related endogenous signaling molecules, maintaining the stability of the internal environment of the body.

Weight loss and PD (Parkinson’s Disease) are currently hot research fields, and NodThera has taken a unique path, using the old target NLRP3 to achieve “one trick to rule them all.”

In February 2024, NodThera published a research article in a journal showing that NLRP3 inhibitors demonstrated weight loss and anti-inflammatory effects in preclinical studies.

In March 2024, NodThera announced positive data from the Phase 1b/2a trial of its NLRP3 inhibitor NT-0796 for the treatment of patients with Parkinson’s disease (PD).

The analysis showed that NT-0796 could reduce key inflammatory and neuroinflammatory biomarkers in the blood and cerebrospinal fluid (CSF) of patients. Currently, preparations for the Phase 1a/2b trial in PD patients are underway.

Four months later (in June 2024), NodThera also found that NT-0796 in the Phase 1a/2b trial could effectively reduce the levels of C-reactive protein (CRP) in patients and significantly reduce their body weight.

The CEO of NodThera said in an interview that the company will advance another candidate drug into the clinic, which is mainly used for PD, while NT-0796 will focus on cardiovascular and metabolic diseases.

12

OMass Therapeutics

OMass Therapeutics was established in 2016 and is a spin-off from the University of Oxford. The company utilizes native mass spectrometry technology for the development of new drugs.

Specifically, OMass’s technology can observe the biology of membrane proteins in their native state, discovering natural allosteric binding sites on these protein targets while preserving non-covalent interactions, thereby screening for lead compounds.

Over the years, new strategies for identifying protein targets have emerged continuously. However, due to issues such as low throughput, difficulty in synthesizing probe molecules, and discrepancies in in situ information between drug molecules and proteins in the body, research often progresses slowly or fails.

In fact, almost all cellular biological processes involve interactions between proteins and other biomolecules (including DNA, RNA, lipids, metabolites, etc.).

Therefore, fully understanding and integrating the information of complex cellular interactions will greatly promote the development of medical technologies such as drug design and disease diagnosis.

OMass’s drug discovery platform, OdyssION™, integrates novel biochemistry techniques, next-generation native mass spectrometry, and custom chemistry, allowing the examination of protein interactions within their native ecosystem while avoiding cellular complexity.

Four years after securing Series A financing, OMass secured another $100 million in Series B financing in 2022.

This round of financing will be used to advance multiple pipelines of the company towards clinical trials, including projects targeting congenital adrenal hyperplasia, inflammatory bowel disease, and widespread inflammation.

It is worth mentioning that among the investors of OMass, there are also GV and Sanofi.

13

ProFound Therapeutics

ProFound Therapeutics was established in 2020 and incubated by the renowned investment organization Flagship. The company is dedicated to exploring the “dark matter” proteins in human cells.

After the completion of the human genome sequencing, research on the human genome sequence has shown that there are approximately 20,000 genes in the genome that encode proteins.

However, in addition to the coding sequences, there is still a large amount of DNA sequence present. Studies have shown that only about 2% of the human DNA sequence is protein-coding, and about 80% of the remaining DNA sequence is transcribed into RNA.

The function of these sequences has not yet been fully revealed, and these proteins of unknown function are referred to as “dark matter.”

Given that human understanding and utilization of proteins only began a few decades ago, there is still a huge space for the development of unknown proteins. One of the most notable examples is the discovery that erythropoietin can treat anemia.

If research finds that there are more than 20,000 protein-coding genes in the human genome and more RNAs are translated into proteins, it would represent a paradigm shift in biology and reveal a whole new universe of treatments and targets.

According to ProFound’s official website, the company has used its ProFoundry™ platform to discover tens of thousands of new proteins, greatly expanding the number of potential therapeutic targets.

In June of this year, the company reached a research and development agreement with Pfizer to use the ProFoundry map to collaborate on the development of new targets for obesity treatment.

14

Recludix Pharma

Recludix Pharma was established in 2019, focusing on discovering protein targets that target the SH2 domain, with therapeutic areas in oncology and inflammation.

The SH2 domain is crucial for regulating the location and activity of proteins and plays a key role in cell signal transduction. Recludix focuses on the STAT proteins around SH2.

STAT proteins are downstream of the JAK/STAT pathway. Therefore, researchers believe that selective STAT inhibitors can produce drugs with stronger targeting and fewer side effects.

Recludix’s core pipeline is a STAT6 inhibitor. In 2023, Sanofi introduced the product rights with a total transaction value of $1.325 billion.

Currently, Recludix has screened a high-affinity lead compound, REX-2787, which is currently being further optimized. The lead compound can already show selective advantages over JAK and TYK2 small molecule inhibitors, comparable to large molecule antibody drugs.

Recludix expects the STAT6 inhibitor to enter Phase I clinical trials by 2025. If the project progresses smoothly, the product is expected to become an oral version of Dupixent.

According to the cooperation agreement, Recludix will advance the STAT6 inhibitor from preclinical research and development to the start of Phase II clinical trials. After that, Sanofi will take over the global clinical development and commercialization responsibilities.

15

Tubulis

Tubulis was founded in 2019 and is committed to the development of a new generation of ADC drugs for the treatment of cancer.

The goal of Tubulis is to innovate in all aspects of ADC development to solve the main bottlenecks in the field and maximize the overall performance of ADCs.

To this end, the company has three technology platforms: P5, Tubutecan, and Tub-tag®.

The P5 platform is a cysteine-selective conjugation that can achieve a uniformity of DAR 8, with excellent linker stability and chemical flexibility, capable of quickly identifying lead compounds.

The Tubutecan platform’s proprietary linker-payload platform provides optimized targeted delivery of potent topoisomerase I inhibitors while reducing unnecessary targeted toxicity.

Effective payload attachment with stable and high DAR values (DAR8) is achieved without affecting the bio-physical properties of the entire ADC molecule.

The Tub-tag® platform is inspired by microtubule biology; TTL can participate in the regulation of microtubule homeostasis by catalytically linking tyrosine to the C-terminus of α-tubulin.

Based on this set of technology platforms, Tubulis has publicly developed 6 research pipelines, 4 self-developed projects, and 2 cooperative projects with BMS and the Swiss biotechnology company Oncoteq.

Among them, the two most advanced pipelines are TUB-040 targeting the tumor antigen Napi2b and TUB-030 targeting 5T4.

In March 2024, Tubulis completed a €128 million Series B2 financing round, one of the main goals of which is to promote the clinical proof-of-concept of these two pipelines.

It is worth mentioning that, together with the €60 million B1 round in 2022, the company’s Series B financing amount reached €188 million.

In terms of transactions, on April 20, 2023, BMS and Tubulis reached a cooperation agreement to use the latter’s P5 conjugation ADC technology platform to jointly develop a new generation of anti-tumor ADC drugs.

Bristol Myers Squibb paid a prepayment of $22.75 million, with a milestone amount of over $1 billion and a certain percentage of sales sharing. In exchange, BMS obtained the rights to exclusively develop “highly differentiated” ADCs using Tubulis technology for the treatment of solid tumors.

【Editor’s note】This is a quick translation of a Chinese artilce posted on DrugTimes media matrix. To read the original article, please click here. Many thanks!