A venture capital firm with offices in the US typically makes equity investments in U.S.-based companies, with portfolio companies located on both coasts and throughout the central part of the country. The firm will consider investing at all stages, with a focus on seed and early-stage investments, including founding companies. Investment size is up to $20 million throughout a portfolio company’s path to liquidity.
The firm is currently looking for new investment opportunities in the life science space, with a specific focus on biopharmaceuticals and therapeutic medical devices. The firm has invested in biopharmaceutical companies focused on developing drugs to treat enteral feeding intolerance and disorders that are driven by CD47-mediated signaling pathways, including leukemia, lymphoma, solid tumors, and pulmonary hypertension. In addition, the firm has invested in a medical device developing a minimally-invasive, catheter-based device to re-create valves in deep leg veins. The firm does not look at diagnostics, though may be interested in technology with real-time feedback for procedures.
The firm focuses on identifying and shaping early-stage life science companies in the series A/B rounds to create significant shareholder value. Because of its extensive operating expertise, the firm is able to help entrepreneurs achieve near-term objectives that position their companies for exit.
If you are interested in more information about this investor and other investors tracked by LSN, please email salescore@lifesciencenation.com.
A U.S. subsidiary of a China-headquartered enterprise focused on advanced manufacturing and technical services, medical and healthcare, trade, and engineering services. The firm is seeking investment opportunities in life sciences and healthcare. The firm is open to various deal structures, including equity investments, M&A, and joint ventures.
For equity investments, the firm’s sweet spots are Series A and Series B, although the firm is capable of making later-stage investments. Typical check sizes range from $10M to $100M. While primarily focused on opportunities in the U.S., the firm is also open to investments in North and South America.
The firm is most interested in biotech therapeutics and pharmaceuticals and remains opportunistic regarding modalities and indications. The firm typically evaluates assets in Phase I or Phase II. Other areas of interest include hospital products, especially those leveraging AI, as well as surgical tools and R&D research technologies.
The firm does not have specific requirements for a company’s founding team.
If you are interested in more information about this investor and other investors tracked by LSN, please email salescore@lifesciencenation.com.
A privately funded investment firm based in Canada is focused on making direct investments in the following business sectors: medical technology, medical clinics, healthcare IT and healthcare real estate. In medtech, the firm seeks to invest in seed stage companies. The firm looks to partner and fund scientific founders to launch a new company and will primarily invest in the seed stage round. The firm typically allocates $100K-$200K, and will syndicate with other investors outside of their region to invest in larger rounds of $500K or more. The firm has physician, medical experience, particularly in the surgical field. The firm invests globally and is currently seeking new investment opportunities.
In the life sciences, the firm is currently seeking to invest in medical devices and healthcare IT. The firm is opportunistic in terms of the class of device and indications, and has particular interest in surgical devices and tools. The firm is additionally interested in digital health, especially those with a software component. The firm prefers to invest in the pre-prototype stage and with particular preference to very early-stage preclinical technology.
The firm is seeking startups with a maximum $5M pre-money valuation and will invest in pre-revenue companies. The firm is very hands-on after an investment, opening up and bringing their network to their portfolio companies.
If you are interested in more information about this investor and other investors tracked by LSN, please email salescore@lifesciencenation.com.
A private family foundation dedicated to advancing brain tumor research employs a venture philanthropy investment model, which combines deep disease-focused expertise with funding for high-risk/high-reward opportunities. The foundation’s fund typically participates in seed to series A financing rounds with initial investment ranging from $250K to $1M and potential for follow-on investments. The fund is looking to make 3-5 investments per year, primarily within the US and Canada. As a subsidiary of the foundation, the fund will leverage the extensive network and expertise of the foundation and is active in supporting their portfolio companies. The fund does not typically lead rounds and more often co-invests.
The fund focuses on primarily on brain tumor and will consider all technology types, including therapeutics, medical devices, and diagnostics. The fund will also consider adjacent spaces such as neuroscience, as long as there are potential implementations in brain cancer. The fund is also open to talking with companies that do not have a pipeline in brain cancer currently but have potential application in brain cancer in the future. The fund seeks to make investments that are impactful for the company, and typically prefers companies in pre-clinical or early clinical stages, especially for therapeutics. For diagnostics, the fund may consider assets that are in later stages of clinical development.
An ideal founding team will have complementary skill sets, and expertise on the business or the fundraising front is a plus.
If you are interested in more information about this investor and other investors tracked by LSN, please email salescore@lifesciencenation.com.
A US-based venture fund invests only in seed and pre-seed rounds, and focuses solely on opportunities in healthcare IT, medtech and consumer health. The firm primarily invests in U.S. based companies but can invest in any geography.
The firm invests in very early stage companies across the healthcare innovation ecosystem, including healthcare IT, medical devices, and consumer health. The firm is highly interested in preventative healthcare, future of work and healthcare IT applications. The firm is open to investing in any area of medicine, but has specific interest in opportunities in cardiology, pulmonary diseases, diabetes, and women’s health.
The firm does not invest in companies that have already raised over $5 million in dilutive capital. The firm seeks to invest in high quality management teams, and prefers to work with experienced entrepreneurs that have a proven track record in their sector.
If you are interested in more information about this investor and other investors tracked by LSN, please email salescore@lifesciencenation.com.
Acceleration of laboratory-based technical and computational cross-fertilization, and ethical and cost pressures on regulatory bodies and therapeutic innovators is driving advancements in preclinical human-based technologies.
Organ (Lab)-on-chip (OoC/LoC)is one of the most striking examples of new translational research technology expansion with ~35% CAGR expected over the next decade (below).
Collaborations between academia and CRO’s are driving improvements in organoid technology for the field of oncology broadly and are expected to improve OoC adoption. Academic innovation using commercial OoC technology is also advancing applications in specific indications in oncology. CRO’s continue to build off established uses in ADME and toxicology to explore R&D applications in oncology space and have even combined organ systems to support elaboration of multiple drug parameters in a single assay.
DEALS
The Tara Biosystems – Valo Health deal is a nice example of how an organ-on-a-chip technology approach has driven collaborations, acquisitions and deals:
Tara Biosystems and GSK collaborate on CV drug profiling (2019)
Valo Health acquires Tara Biosystems for CV OoC platform (2022, ~$75M upfront)
Valo and Novo Nordisk sign CV drug discovery deal (2023, $60M upfront, $2.7B total)
Emulate, TissUse and Mimetas have also been backed by strong big pharma collaborations (AstraZeneca, Bayer, Roche) and funding rounds.
Drug development efforts targeting the constitutive 26S proteosome have led to the development of several important multiple myeloma (MM) and mantle cell lymphoma treatments, including the first landmark FDA approval of Millennium Pharmaceuticals’ (now Takeda) dipeptide boric acid Velcade (bortezomib) in 2003 and second-generation molecules, such as Amgen/Ono Pharmaceutical’s irreversible inhibitor Kyprolis (carfilzomib) and Takeda’s orally available inhibitor Ninlaro (ixazomib). Second-generation versions of these ‘pan-proteosome’ drugs have longer duration of effect, reduced peripheral neuropathy and increased safety in renally impaired patients, but may cause gastrointestinal and cardiac toxicity. This toxicological profile has shifted attention to developing inhibitors selective for an alternative form of the core 20S proteosome—the immunoproteasome, which processes peptides for presentation to CD8+ T cells in the MHC-I complex and is constitutively expressed only in hematopoietic cells, induced in immune cells stimulated in the presence of IFN-γ, and upregulated in certain cancers like MM.
The β1 subunit (particle components beta subunit 6; PSMB6), β2 subunit (PSMB7), and β5 subunit (PSMB5) found in the constitutive 26S proteasome (left) are replaced in the immunoproteasome (right) by the β1i subunit (low molecular mass polypeptide 2 (LMP2)/PSMB9), β2i subunit (multicatalytic endopeptidase complex-like 1 (MECL-1)/PSMB10), and β5i subunit (LMP7/ PSMB8), respectively. Existing inhibitors and their sites of action are indicated. Adapted from https://bit.ly/4kgmQj9
Currently, Kezar Life Sciences’ is furthest along in development; in April, it completed a phase 2a trial in autoimmune hepatitis of zetomipzomib (KZ-616), a small-molecule that inhibits both the immunoproteasome core particle component beta subunit 8 (PSMB8; LMP7/β5i) and PSMB9 (LMP2/β1i). Merck kGaA (Darmstadt, Germany) is also pushing forward with a phase 1 clinical program of M3258, a small-molecule inhibitor specific for PSMB8 and intended for use in MM (Principia Biopharma’s selective PSMB8 inhibitor was swallowed up by Sanofi in 2020 when the pharma acquired the San Francisco-based biotech’s Bruton’s tyrosine kinase inhibitor program). Elsewhere, Leiden University startup iProtics recently received a €200K grant from the Dutch Biotech Booster to develop selective immunoproteosome inhibitors, while Auburn University spinout Inhiprot (West Lebanon, NH) received SBIR funding to develop a dual PSMB6/PSMB9 inhibitor for MM. Now, a new study reveals immunoproteosome targeting may also have benefits in neuroinflammatory diseases like multiple sclerosis.
The work, published in Cell and led by Catherine Meyer-Schwesinger and Manuel Friese, from University Medical Center Hamburg-Eppendorf, identifies a neuron-intrinsic mechanism of neurodegeneration in multiple sclerosis (MS) driven by the immunoproteasome.
Under healthy conditions, neurons utilize the constitutive proteasome subunit PSMB5 to regulate proteostasis and degrade 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), a potent stimulator of glycolysis. This degradation is key because neurons rely more on the pentose phosphate pathway than on glycolysis to produce antioxidants like NADPH and glutathione for protection against oxidative stress.
However, Meyer-Schwesinger, Friese and their colleagues show that, during neuroinflammation, chronic exposure to interferon-γ leads to the induction of the immunoproteasome in neurons, triggering the replacement of constitutive proteosome PSMB5 (β5c) with PSMB8 (β5i). This subunit swap in neurons reduces proteasomal activity, resulting in accumulation of PFKFB3, which in turn enhances glycolysis, diminishes the activity of the pentose phosphate pathway, and impairs redox homeostasis — conditions that sensitize neurons to oxidative injury and ferroptosis.
Interferon-induced immunoproteasome markedly decreases proteasomal activity in neurons, leading to a switch in neuronal metabolism from oxidative phosphorylation (left) to glycolysis accompanied by oxidative injury and ferroptosis (right). Source: Cell
The team showed that this mechanism was operational in both experimental autoimmune encephalomyelitis (EAE; a mouse model of MS) and brain tissue from MS patients. Moreover, neuron-specific knock-out of Psmb8 or pharmacological inhibition using the small-molecule PSMB8 inhibitor ONX-0914 (originally developed at Onyx Pharmaceuticals/Proteolix) protected neurons in vivo from inflammation-induced damage. Similarly, blocking PFKFB3 with the small-molecule inhibitor PFK-158 or through conditional knockout in neurons reduced disease severity in EAE, prevented neuronal and synaptic loss, and reduced markers of oxidative stress and lipid peroxidation.
It is important to highlight that, unlike cancer or immune cells, neurons do not upregulate PSMB8 in response to a series of MS-related cytokines. So, the neuron-specific effect reported in this study might only become active upon chronic neuroinflammation (i.e. chronic exposure to interferon-γ). Understanding this mechanism might reveal new targets related to the immunoproteosome in the treatment of MS.
This brings us to challenges for translational efforts seeking to develop immunoproteosome inhibitors against MS. Several important neuronal processes, such as synaptic transmission and calcium signaling, are tightly linked to proteasome function; thus, pan-proteosome inhibitors like Velcade could be detrimental to the CNS. The saving grace of approved proteosome inhibitors is that current chemotypes (boronate-based peptides or epoxyketone-based binders) do not cross the blood brain barrier, at least in healthy individuals. Thus, any MS program might need to use intrathecal injection for compounds derived from existing chemical series or engage a medicinal-chemistry effort to design molecules that can breach the BBB and retain potency.
The gambit for immunoproteosome-selective drugs is that they avoid inhibiting constitutive 26S proteosome activity in most tissues (and non-inflammed CNS), which is what makes Velcade and its derivatives so difficult for patients to tolerate; an immunoproteosome inhibitor should therefore have a more favorable safety profile. But so far, immunoproteosome-targeting drugs have had their own share of toxicity problems in the clinic.
Last October, Kezar abandoned its program for zetomipzomib in lupus nephritis after the FDA placed a clinical hold on the trial after 4 patient deaths. The agency placed a second partial hold on the company’s autoimmune hepatitis trial in 24 patients last November due to concerns about steroid control and injection site reactions in 4 patients who were waiting to roll over into the open-label extension arm. Concerns about compromised immune surveillance of acute or latent viral infections due to hobbled antigen processing and presentation would also need to be explored.
In sum, the new work provides strong evidence that the immunoproteosome plays a key role not only in inflammation or infiltration of immune cells, but also in a metabolic switch in neurons which is a key driver of vulnerability in MS. It will be interesting to see whether either targeting immunoproteosome component PSMB8 or taking a completely different tack, blocking PFKFB3, will prove more practical as a neuroprotective strategy in MS.
The firm is focused on therapeutics companies and does not invest in medical devices, diagnostics, or digital health. The firm is open to considering assets of very early stages, even those as early as lead optimization phase. The firm considers various modalities, including antibodies, small molecules, and cell therapy. Currently, the firm is not interested in gene therapy. Indication-wise, the firm is most interested in oncology and autoimmune diseases but has recently looked at fibrotic diseases and certain rare diseases as well.
The firm is opportunistic across all subsectors of healthcare. Within MedTech, the firm is most interested in medical devices, artificial intelligence, robotics, and mobile health. The firm is seeking post-prototype innovations that are FDA cleared or are close to receiving clearance. Within therapeutics, the firm is interested in therapeutics for large disease markets such as oncology, neurology, and metabolic diseases. The firm is open to all modalities with a special interest in immunotherapy and cell therapy.
A strategic investment firm of a large global pharmaceutical makes investments ranging from $5 million to $30 million, acting either as a sole investor or within a syndicate. The firm is open to considering therapeutic opportunities globally, but only if the company is pursuing a market opportunity in the USA and is in dialogue with the US FDA.
The firm is currently looking for new investment opportunities in enterprise software, medical devices, and the healthcare IT space. The firm will invest in 510k devices and healthcare IT companies, and it is very opportunistic in terms of indications. In the past, the firm was active in medical device companies developing dental devices, endovascular innovation devices, and women’s health devices.
A venture capital firm founded in 2005 has multiple offices throughout Asia, New York, and San Diego. The firm has closed its fifth fund in 2017 and is currently raising a sixth fund, which the firm is targeting to be the largest fund to date. The firm continues to actively seek investment opportunities across a […]
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