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7 Hills Pharma LLC
- 2450 Holcombe Blvd, Suite J, Houston, Texas 77021, US
- http://www.7hillspharma.com
Company Contact:
Legal Entity Type: LLC
Company Type: Pharmaceutical
Company Stage: Development
No. of Employees: 6
Desired Financial Amount: $20 million
Background
Company Background
7 Hills CEO Upendra Marathi is an established Houston-based pharma executive and developer. Following the successful transition of Upendra’s previous project, PLx Pharma, to the public markets, he was teaching a biotech entrepreneurship class when he met Peter Vanderslice and the team at Texas Heart Institute (THI). An expert in integrin antagonist small molecule synthesis and development, Peter, Darren Woodside, and colleagues had recently conceptualized and created a novel small molecule selective integrin agonist, initially imagined as a way to improve stem cell therapies in heart-related indications. Upendra realized that such an agonist might also be used to improve the effectiveness of immunotherapies such as vaccines and checkpoint inhibitors by increasing immune cell adhesion at rate-limiting steps in the antigen-specific immune response. After licensing THI’s original technology, 7 Hills identified a lead molecule, 7HP349, brought it through preclinical development, and completed a Phase I clinical trial that demonstrated an exceptional safety profile and oral bioavailability. 7 Hills has also identified additional classes of novel integrin agonists, a selection of which are in preclinical development as next-generation immunomodulators. In parallel, 7 Hills has continuously enhanced its pioneering patent estate to build durable competitive advantage and barriers to entry covering the broad range of potential applications for selective integrin activation as a novel mechanism for immune stimulation.
Management
Upendra Marathi, PhD, MBA, President & CEO, is the founder, investor, and an inventor of 7HP technology. He has led the development of three novel pain and cardiovascular drugs, including one which has recently been approved by the FDA. He co-developed one of the first genetically modified stem cells to improve bone marrow function in chemotherapeutic patients. As a venture capitalist, he was involved in the founding and launch of several biotechnology companies. He has helped raise over $50 million in equity financing. Upendra was a post-doctoral fellow at St. Jude Children’s Research Hospital and M.D. Anderson Cancer Center, and earned a Ph.D. in Pharmacology from Loyola University Chicago. Upendra has an M.B.A. from Rice University and has served as a faculty member.
Lionel Lewis, MA, MB BCh, MD, Chief Medical Officer, is an experienced solid tumor trialist who has worked on 40 Phase I trials, and led 10 first-in-human studies including immune checkpoint inhibitors. Currently he co-directs co-directs the Norris Cotton Cancer Center (NCCC) at Dartmouth Molecular Therapeutics Program and the NCCC Phase-I group, and is Director of the Clinical Pharmacology Shared Resource and Medical Director of the Dartmouth Clinical Trials Office. He is also the current Executive Director of the American Board of Clinical Pharmacology and the vice chair of the Pharmacogenetics and Population Pharmacology (PPP) committee of the Alliance of Clinical Trials in Oncology, an NCI intergroup. He has served on and chaired several DOD and NIH study section panels. He has published more than 150 peer reviewed manuscripts in the field of clinical pharmacology and has edited/co-authored several textbooks in the field.
William Schary, PhD, Vice President of Clinical and Regulatory Affairs, has extensive experience as a development, clinical and regulatory scientist and biopharmaceutical industry executive. He is a former clinical reviewer for the U.S. Food and Drug Administration, has served in senior roles in global clinical and regulatory functions with Abbvie Inc. and Takeda Pharmaceutical Co., and has held executive management positions at a number of biotech companies. He has designed and successfully executed drug development plans resulting in the acceptance of global dossiers for investigational products, including approval of more than 20 drug and medicinal products across multiple therapeutic areas. He also established the procedures and managed operations of a Phase 1 clinic unit as well as coordinated efforts at academic and commercial research centers for implementation of new drug development and new drug regulatory and quality assurance programs.
Board of directors
Michael S. Perry, DVM, PhD, Chairman, joined 7 Hills Pharma’s Board of Managers in July 2021. Dr. Perry brings extensive experience across the global pharmaceutical value chain for healthcare products spanning diverse therapeutic areas. In his career, he has been materially involved in the successful development and commercial launch of more than 30 prescription products, 14 of which achieved blockbuster status. Dr. Perry is currently the Chief Executive Officer of Avita Medical (NASDAQ:RCEL and ASX:AVH) and has previously served in a variety of pharmaceutical executive roles, including as Chief Scientific Officer of Novartis’ Cell and Gene Therapy Unit from 2014-2017 and Vice President and Global Head of Stem Cell Therapy for Novartis Pharmaceuticals Corp. from 2012-2014. He also served as President and Chief Medical Officer of Poniard Pharmaceuticals, Chief Development Officer at VIA Pharmaceuticals, Chairman and Chief Executive Officer of Extropy Pharmaceuticals, Global Head of Research and Development for Baxter’s BioScience Division, President and Chief Executive Officer of both SyStemix Inc. and Genetic Therapy Inc., and Vice President of Regulatory Affairs for Novartis Pharma. Additionally, he served in executive roles at Syntex Corporation (now Roche) and at Schering-Plough (now Merck). Dr. Perry holds a BSc in Physics, Doctor of Veterinary Medicine (DVM), and a PhD in Biomedical Pharmacology from the University of Guelph, Ontario, Canada. He is also a graduate of the International Management Program at Harvard Business School and serves as Adjunct Professor at the University of Colorado Anschutz Medical Campus, Gates Center for Regenerative Medicine.
Joseph Bailes, MD, Advisor & Manager, is a medical oncologist with substantial experience in legislation, public policy and advocacy, as well as the business aspects of the practice of oncology and medicine. Dr. Bailes has served in various executive leadership capacities for the American Society of Clinical Oncology (ASCO), including terms as President, Interim Executive Vice President and Chief Executive Officer, and Chair of the ASCO Government Relations Council. He has also served as the Executive Vice President of Clinical Affairs for US Oncology, Inc. Dr. Bailes received his medical degree from the University of Texas Southwestern Medical School at Dallas.
Kala Marathi, Co-Founder & Manager, is the Managing Director of the Cougar Venture Fund, a Lecturer in Venture Capital Investing at the University of Houston, and COO of Skypoint Capital, an investment firm that focuses on income producing assets. She has more than 20 years of operating and financial experience. In her role as Managing Director of the Houston Angel Network, Kala has facilitated over $30M in investments in 85 deals and co-founded the Texas Halo Fund. Kala was a founding member of Reliant Energy Net Ventures, the corporate venture arm of Reliant Energy. At Reliant, she led several smart grid pilots and technology initiatives, and launched a subsidiary called Texas Star Energy. She also has extensive experience in strategy and corporate finance with such firms as Continental Airlines and Chase. Kala has served on the Board of Directors of the Texas Lyceum and the National Association of Women MBAs (Houston Chapter), and served as co-chair of the HX Cybersecurity Technology Committee. Kala has B.A. in Japanese and Economics from Wellesley College, and an MBA from the Amos Tuck School of Business at Dartmouth College.
Richard Dixon, PhD, Co-founder & Manager, is an experienced pharmaceutical executive who has founded and invested in new ventures and also has led numerous commercial programs, which have resulted in four approved commercial products including Argatroban, Crixivan and Singulair. He co-founded and served as CSO of Encysive Pharmaceuticals (ENCY) and sold the business to Pfizer for ~$400 million. Prior to that, he held various management positions, including head of the molecular biology department at Merck and Co (MSD). Dr. Dixon’s research groups have produced more than 10 new chemical entities which have entered human testing. He has a Ph.D. in Virology from Baylor College of Medicine and conducted postdoctoral research at Johns Hopkins University School of Medicine in the laboratory of Dr. Daniel Nathans, the 1978 Nobel Laureate in Medicine.
Product / Service
disease area / application
Improve the effectiveness of immunotherapies, including infectious disease vaccines (e.g., influenza, tuberculosis, COVID-19, Chagas disease) and immune checkpoint inhibitors for solid tumors.
product / Service
Among infectious disease vaccination indications, we are initially targeting geriatric influenza due to its large size and persistent, significant unmet needs. Americans aged ≥65 years accounted for 57% and 75% of all influenza-related hospitalizations and deaths, respectively, in the 2019-20 season, despite a vaccination rate of ~68%. A key factor for suboptimal vaccine effectiveness in the elderly is immunosenescence, the gradual decline of immune function with age. Prolonged cell adhesion is essential for effective antigen presentation and T cell priming at the immune synapse between antigen presenting cells (APCs) and naïve T cells, as well as for T cell memory and effector functions. One impact of immunosenescence is a progressive reduction in ICAM-1 induction on activated dendritic cells which, by decreasing T cell priming, may lead to suboptimal vaccine effectiveness in the elderly. 7HP349 is a first-in-concept, oral, small-molecule allosteric α4β1/αLβ2 activator that may promote APC-T cell adhesion and improve T helper function to increase the effectiveness of geriatric influenza vaccination. Outside of geriatric influenza, preclinical studies have demonstrated the ability of 7HP349 to also augment vaccines against tuberculosis, SARS-CoV-2, and Chagas disease. The broad preclinical utility observed, coupled with our novel mechanism of action, suggest that 7HP349 and pipeline molecules may be capable of augmenting potentially any infectious disease vaccine, regardless of antigen or platform technology, unlocking a variety of additional large and valuable markets, such as shingles and pneumococcal vaccination.
While immuno-oncology (IO) drugs for solid tumor cancers, such as PD-1/L1 and CTLA-4 immune checkpoint inhibitors (ICIs) have induced remarkable response rates in patients with advanced melanoma and other solid tumors, 43% of metastatic melanoma patients on 1st/2nd line aPD-1/L1 therapy are resistant, with limited treatment options. Current standard of care with dual checkpoint blockade only provides ~20% ORR in this patient population. A primary cause for the lack of efficacy of ICIs is insufficient priming of T cells and their homing to tumors. Integrin-mediated firm adhesion to the vascular endothelium is an essential prerequisite for T cell activation, extravasation of immune cells into tumors, and stabilization of the killing synapse. 7HP349 activates α4β1 and αLβ2 integrins, facilitating engagement with their counter ligands, VCAM-1 and ICAM-1, respectively, enhancing T cell activation, trafficking and cytolytic function. 7HP349, in combination with ICIs, may offer market-beating anti-tumor efficacy with no added toxicities. With success in resistant melanoma, 7 Hills will potentially unlock many other oncology indications, such as lung, breast, and bladder cancers.
technology / ip
7 Hills Pharma was the first company to conceptualize the use of selective integrin activation to augment the antigen-specific immune response. To maximize our first-mover advantage, we have continually invested in cornering this potentially large and valuable market. Our broad and pioneering patent portfolio includes claims covering the composition of our novel integrin agonists, their use in combination with vaccines and checkpoint blockade, and additional aspects of the technology providing durable barriers to entry into the 2040s. Our IP has been positively reviewed and vetted by a variety of public and private organizations ranging from state and federal government agencies to venture capital groups.
distribution channels
7 Hills plans to license developmental assets to large pharma partners in exchange for upfront, milestone, and royalty payments. These partners will complete development and commercialization of 7HP349 and/or other out-licensed integrin activators for one or more specific medical indications. We have maintained substantive dialogs with potential licensees, and those discussions have highlighted the critical threshold for deal-making: demonstrating that 7HP349 augments immunogenicity within an initial target population (e.g., geriatric influenza vaccinees, aPD-1-resistant melanoma patients). We plan to cross that threshold with our next clinical trial, whether in solid tumors or infectious disease. We have a trial designed for each option and are raising funds to support those trials. Analysis of comparable transactions suggests that a licensing transaction in either therapeutic area may demand an upfront payment of >$50MM, milestones of >$700MM, and low double-digit royalties on commercial sales. Alternatively, 7 Hills may be sold in its entirety to a well-positioned and well-resourced partner to continue development and commercialization of our platform technology in various indications spanning a range of therapeutic areas.
market size
The market potential for 7HP349 across infectious disease and oncology indications is very large. Since our compounds may be able to augment potentially any antigen-specific immune response, the range of potential applications is broad and valuable. Geriatric influenza vaccination, our initial target in infectious diseases, yields an estimated demand of >30MM doses per year in the US alone, offering well over $1 billion/year in potential peak sales revenue from the domestic market. Growth in this market is expected to be strong and consistent over the next couple of decades. According to the United Nations, by 2050, the global population >65 years will approximately double from ~800MM to ~1.6 billion. These elderly individuals will need safe immune augmentation not only to protect them against influenza, but a variety of other pathogens. Each additional infectious disease indications is expected to offer at least $1 billion in peak sales potential.
Anti-PD-1-resistant melanoma, our initial target among many potential oncology indications, is another >$1 billion opportunity. In the US alone, resistant melanoma could offer $250-500MM/year in peak sales potential. By 2040, the incidence of melanoma is expected to grow by over 50%, suggesting that this indication will only grow in demand in the coming decades. A large pool of additional oncology indications may be unlocked with successful clinical data in melanoma, including lung, breast, bladder, and other cancers. Each additional oncology indication offers $500MM to >$1 billion in peak sales potential.
competition
In oncology, while there are many approaches to augmenting frontline aPD-1, there is clear opportunity in 2nd Line or 3rd Line patients who developed secondary resistance following aPD-1 therapy. Based on reported data, we estimate approximately 90% of patients with solid tumors are resistant to aPD-1 based therapies. In melanoma, 40-65% are resistant to aPD-1 based therapy. There are no direct competitors to 7HP349 targeting activation of α4β1 and αLβ2. 7 Hills is the first to conceive of and use integrin activators to improve checkpoint inhibition (CPI). While there is intense competition in augmenting 1L aPD-1/L1, there are a limited number of pure play programs targeting aPD-1-resistant melanoma. The majority of these programs focus on cell therapies and intratumoral administration of therapeutic agents, expensive and error-prone processes that deliver higher treatment costs, complexity, and often toxicities while decreasing patient access when compared to a safe and orally-delivered immunostimulant like 7HP349. As resistance to CPI is fundamentally a priming problem, the major developmental drivers include augmentation of T cell co-stimulation (Relatlimab), increasing immunogenic cell death (Ceralasertib), antigen presenting cell (APC) activation (CD40L, TLRs), and T cell recruitment (Lavatinib), which indirectly augments integrin function by inducing the expression of VCAM-1 and ICAM-1 on tumor endothelium. The importance of ICAM-1 engagement is further underscored by the Catalum GmbH Phase I program on a GDF-15 inhibitor, CTL-002, an indirect β2 integrin activator that is expected to improve T cell activation and trafficking that has shown ~25% ORR in aPD-1-resistant patients. Importantly, Netherlands Cancer Institute has recently announced that in Phase III testing (M14TIL), autologous tumor infiltrating lymphocyte (TIL) therapy has shown 49% ORR. However, this approach may have limited market penetration due to the complex logistics of TIL production.
In infectious disease, although integrin-mediated cell adhesion is essential for an immune response, there are no direct competitors of 7HP349 targeting α4β1 (VLA-4) and αLβ2 (LFA-1) integrins. 7 Hills is the first to conceive and use integrin activators to improve checkpoint inhibition and infectious disease vaccines. Indirect competitors include influenza vaccines that elicit a strong enough immune response that will not require immune stimulation, or admixed vaccine adjuvants or immune stimulants that effectively improve immune response. Adjuvant competitors include Dynavax CpG 1018, Novartis MF59, and GSK AS01. 7HP349 is the only oral immune stimulant in development for use with any influenza vaccine, and has shown in multiple preclinical models to systemically augment both cellular and humoral immunity. It should be noted that 7HP349 may be synergistic with any of the competitors’ admixed adjuvants to safely elicit both local and systemic cellular and humoral immune responses. 7 Hills Pharma compounds are differentiated from the standard adjuvant approach in multiple dimensions. First, 7 Hills compounds, such as 7HP349, are allosteric activators of integrins, and facilitate integrin interactions with their cognate ligands. They are not direct activators of receptors like pattern recognition receptors, and as such, the approach may have an improved systemic safety profile than compared to direct immune modulators. Secondly, unlike conventional adjuvants, 7HP349 is delivered orally, eliminating the need to co-formulate it with a vaccine, decreasing cost, complexity, and time-to-market. Instead, 7HP349 can be stockpiled and dosed in parallel with potentially any vaccine, a unique capability that also unlocks a variety of biodefense applications. Thirdly, competitive compounds facilitate adjuvantation that may be restricted to lymph nodes proximal to the vaccination site. As a systemic drug, 7HP349 may augment systemic adaptive immune responses and may not be limited to the local draining lymph nodes at the site of vaccination. Finally, cell-mediated immunity contributes to improvement of influenza vaccines. Unlike conventional adjuvants, 7HP349 has the potential to augment both humoral and cellular immunity. Looking to the future, universal flu vaccines and more immunogenic vaccines will be critical for reducing the severity of flu seasons. However, vaccine effectiveness will remain limited until an adjuvant such as 7HP349 is available to augment the immune system and compensate for the immunosenescence observed in the elderly.
Financials
Desired financial amount
$20 million
previous funding
7 Hills has supported its operations from launch through angel funds supplemented with government grants. To date, the company has raised ~$7MM in direct angel investment. In parallel, 7 Hills has garnered ~$13MM in funding from a variety of granting agencies within NIH (e.g., NCI, NHLBI, NIAID), with the company accruing a track record of a high success rate for applications coupled with strong and efficient execution. In addition to financial support, the external vetting and validation of our novel approach and technology that these funding agencies have provided through their granting processes has been invaluable.
current financials
7 Hills has a range of strategic plans available to allow our development programs to progress in a variety of financial scenarios. As such, our burn rate is flexible from ~$50-100k per month. Using current cash, we have a runway into approximately 4Q2023 while progressing at a reasonably rapid pace. However, we have contingency plans to allow the company to continue operations considerably further without additional funding, as well as alternative plans to maximize our speed of development and deal-making with additional funds.
financial use
This funding will be used to reach one or more significant value inflection points in the enterprise value of 7 Hills. Specifically, those thresholds are human immunogenicity data from a Phase Ib or IIa clinical trial showing augmentation of geriatric influenza vaccination and/or checkpoint blockade in resistant melanoma. Depending on outcomes of pending grant applications and the amount of capital raised in this round, 7 Hills has a number of options. First, we may use some of the incoming capital as matching corporate funds required to execute our Phase Ib/IIa clinical trial in resistant melanoma. Positive data from that study, available within 2-3 years of initiation, would facilitate the culmination of an out-licensing deal, according to guidance from potential industry partners.
Alternatively, if certain pending grants are not awarded, we may use the capital raised in this round to execute a Phase Ib/IIa clinical trial using 7HP349 to augment geriatric influenza vaccination. As in the cancer program, success in this trial would facilitate deal-making with large pharma partners, but with a shorter timeline, perhaps within 1.5-2 years of study initiation.
Regardless of the chose clinical path, we will also use funds from this round to progress development of next-generation pipeline compounds through preclinical studies, further broaden and strengthen our pioneering IP portfolio, and bring in additional talent to help manage our expanded clinical and regulatory efforts.
revenue
7 Hills plans to license developmental assets to large pharma partners in exchange for upfront, milestone, and royalty payments. These partners will complete development and commercialization of 7HP349 and/or other out-licensed integrin activators for one or more specific medical indications. We have maintained substantive dialogs with potential licensees, and those discussions have highlighted the critical threshold for deal-making: demonstrating that 7HP349 augments immunogenicity within an initial target population (e.g., geriatric influenza vaccinees, aPD-1-resistant melanoma patients). We plan to cross that threshold with our next clinical trial, whether in solid tumors or infectious disease. We have a trial designed for each option and are raising funds to support those trials. Analysis of comparable transactions suggests that a licensing transaction in either therapeutic area may demand an upfront payment of >$50MM, milestones of >$700MM, and low double-digit royalties on commercial sales. Alternatively, 7 Hills may be sold in its entirety to a well-positioned and well-resourced partner to continue development and commercialization of our platform technology in various indications spanning a range of therapeutic areas.
exit strategy
7 Hills plans to license developmental assets to large pharma partners in exchange for upfront, milestone, and royalty payments. These partners will complete development and commercialization of 7HP349 and/or other out-licensed integrin activators for one or more specific medical indications. We have maintained substantive dialogs with potential licensees, and those discussions have highlighted the critical threshold for deal-making: demonstrating that 7HP349 augments immunogenicity within an initial target population (e.g., geriatric influenza vaccinees, aPD-1-resistant melanoma patients). We plan to cross that threshold with our next clinical trial, whether in solid tumors or infectious disease. We have a trial designed for each option and are raising funds to support those trials. Analysis of comparable transactions suggests that a licensing transaction in either therapeutic area may demand an upfront payment of >$50MM, milestones of >$700MM, and low double-digit royalties on commercial sales. Alternatively, 7 Hills may be sold in its entirety to a well-positioned and well-resourced partner to continue development and commercialization of our platform technology in various indications spanning a range of therapeutic areas. A reasonable estimate for deal-making is 2-3 years from the initiation of our next clinical trial, whether in melanoma or influenza.