ARCH Top-tier Pharmaceutical Venture Capital Firm: ARCH

The R&D of new drugs is inextricably linked to substantial financial backing. Within this framework, the role of venture capital firms is immeasurable. Today, we spotlight the renowned venture capital entity, ARCH.

ARCH Venture Partners, henceforth referred to as ARCH, was established in 1986. Over the years, it has positioned itself within the biotechnology sector by investing in several leading enterprises. These include the RNA therapeutics behemoth Alnylam Pharmaceuticals, gene therapy pioneer Bluebird Bio, CAR-T cell therapy innovator Juno Therapeutics, and base editing front-runner Beam, among others. ARCH stands out as one of the most prolific early-stage investors in the biotechnological domain. Beyond these well-known pharmaceutical companies, which burgeoning stars has ARCH supported?

Lyell Immunopharma: T-cell Therapy Development for Solid Tumors

Inaugurated in 2018 in San Francisco, California, Lyell Immunopharma is a preclinical stage biotechnological firm focused on the development of T-cell therapies for solid tumors. Distinguishing itself from conventional cell therapy enterprises, Lyell endeavors to fundamentally enhance the characteristics of T-cells essential for the treatment of solid tumor patients. This includes overcoming challenges such as T-cell exhaustion and loss of stemness, aiming to address barriers limiting cell persistence, reliability, and therapeutic efficacy.

The company surmounts these challenges through proprietary epigenetic and gene reprogramming technologies. Presently, Lyell has established two proprietary cell reprogramming technology platforms: Gen-R and Epi-R. Gen-R principally addresses T-cell exhaustion; Epi-R is utilized to generate T-cell populations characterized by enduring stemness.

Currently, Lyell is advancing new therapies based on these platforms, aiming to produce innovative, lasting, and potentially curative clinical approaches.

Arbor Biotechnologies: Gene Editing Company Co-founded by Zhang Feng

Established in 2016, Arbor Biotechnologies is a gene editing enzyme development company, co-founded by the esteemed scientist Zhang Feng. Arbor has developed seven gene editing enzymes capable of targeting over 90% of the genome and has identified more than 60 nuclease families and over 70 CRISPR transposases. The company's most advanced project is an in vivo gene editing therapy for Primary Hyperoxaluria (PH), ABO-101, currently at the IND enabling stage.

Verve Therapeutics: Pioneers in Base Editing Therapy

Conceived by the distinguished cardiologist Sekar Kathiresan, Verve Therapeutics is committed to developing preventive therapies for heart diseases through base editing technology. This approach envisages a one-time injection for the permanent prevention of heart diseases.

Verve's candidate, Verve-101, is the inaugural in vivo base editing therapy to enter clinical trials. It leverages lipid nanoparticles (LNP) to deliver the mRNA of an adenine base editor and gRNA targeting the PCSK9 gene. Upon injection, these nanoparticles are absorbed by liver cells, allowing the base editor to enter the nucleus and modify the specific sequence of the PCSK9 gene from A·T to G·C. This modification leads to the shutdown of gene expression, preventing the production of PCSK9 protein by liver cells, thus averting cardiovascular diseases.

In a phase 1b clinical trial, Verve-101 demonstrated a dose-dependent trend in reducing harmful low-density lipoprotein cholesterol (LDL-C) in patients with Familial Hypercholesterolemia (HeFH). A single administration of 0.6mg/kg of Verve-101 reduced LDL-C levels by 55%, with the effect persisting for over 180 days.

Verve plans to initiate a phase I clinical trial for another in vivo gene editing drug, Verve-101, in the first half of 2024, followed by a randomized, placebo-controlled phase II clinical trial for Verve-101 or Verve-102 in 2025.

hC Bio: Specializing in tRNA Drug R&D

hC Bioscience (hereinafter referred to as hC Bio) is a pharmaceutical R&D corporation concentrating on tRNA therapies aimed at addressing protein functionality disorders. tRNA (transfer RNA) constitutes an RNA molecule composed of 76-90 nucleotides, wherein its 3' end is capable of attaching a specific amino acid, a process catalyzed by aminoacyl-tRNA synthetase. Throughout the translation process, tRNA facilitates the transportation of the corresponding amino acid to the ribosome for polypeptide synthesis by recognizing mRNA codons through its anticodon.

hC Bio is advancing two complementary platforms. The first, termed the PTCX (Patch) platform, is deployed to rectify protein functionality disorders induced by nonsense mutations (or "premature termination codons" (PTC)), which result in the premature termination of peptide chain synthesis, leading to incomplete and dysfunctional proteins. Such mutations are linked to 10%-15% of human diseases. The PTCX platform employs engineered tRNA to identify these nonsense mutations within mRNA transcripts, incorporating an amino acid to correct this error, thereby generating the correct full-length protein.

The second platform, designated as SWTX (Switch), targets diseases caused by missense mutations. These mutations occur when a codon encoding one amino acid is substituted by a codon for another amino acid, leading to alterations in the amino acid type and sequence within the polypeptide chain. Many protein abnormalities arise from missense mutations. The SWTX platform is utilized to label pathogenic proteins for subsequent destruction.

Presently, the most significant challenge confronting tRNA therapy encompasses delivery mechanisms. Adenovirus vectors and lipid nanoparticles (LNP) remain the preferred delivery systems among companies engaged in the development of tRNA therapies. Concurrently, investigations into DNA plasmid-based delivery systems are ongoing.

Basking Biosciences: RNA Aptamer Therapeutic Translation Research

Basking Biosciences is a clinical-stage biopharmaceutical entity devoted to the development of novel acute thrombolytic therapies for stroke treatment, focusing on the translational research of RNA aptamer therapy.

BB-031 represents Basking Biosciences' reversible RNA aptamer thrombolytic therapy, specifically designed to address thrombosis by targeting the von Willebrand factor (vWF), characterized by its rapid onset of action and short duration. Preclinical researches indicate that BB-031 can re-establish blood flow in arteries occluded by thrombosis up to 6 hours following a stroke event.

Results from Phase I trials have demonstrated BB-031's favorable safety and tolerability profile, with no reports of serious adverse events within the study. A Phase II clinical trial is anticipated to commence in the first half of 2024.

ARCH exhibits a preference for pioneering technological domains, including in vivo cell therapy, base editing therapy, tRNA therapy, and cell regeneration therapy, Indications are concentrated on tumor and central nervous system diseases, among others. As a seasoned investment institution within the medical sector, ARCH has supported the development of numerous startup companies over the past three decades. The portfolio of companies invested in by ARCH provides valuable insights, underscoring the paramount importance of innovation.

References:

1. https://www.sec.gov/Archives/edgar/data/1993469/000199346923000003/xslFormDX01/primary_doc.xml.

2. https://endpts.com/arch-allied-an-venture-partners-raises-200m-to-build-biotechs-out-of-research-from-japan/.

3. https://ir.vervetx.com/news-releases/news-release-details/verve-therapeutics-announces-interim-data-verve-101.

About the Author:

Yefenghong

Ye Fenghong, a medical editor specializing in oncology at a healthcare internet company, has conducted in-depth research on the pathogenesis and clinical treatment of lung cancer and breast cancer. She has previously been involved in the design and synthesis of anti-tumor drugs and has some experience in computer-aided drug design. She is currently devoted to introducing cutting-edge cancer treatment drugs to a wide range of readers, aiming to help more people avoid cancer pain and embrace good health.