Longevity Biotech is a leading biotech company developing a new class of therapeutic compounds.
Evolution has developed natural defense mechanisms to combat disease, therefore, many diseases are a result of either an overactive or defective signaling pathway. Longevity Biotech is working to develop specific modulators of these pathways in order to leverage the body’s natural processes.
Drugs fall into two main categories, Small Molecules and Biologics, each with their own benefits and liabilities. Small Molecules are typically taken in pill form and often work generically throughout the body, via simple molecular interactions. In contrast, biologics are typically delivered as frequent injections into patients and are considerably more targeted in their mechanism of action, primarily due to their complex surfaces.
Our Hybridtides® combine the targeting abilities of biologics with the stability of small molecules by building from a breakthrough molecular scaffold discovered in Professor Samuel Gellman’s lab at the University of Wisconsin.
By ‘rebalancing’ the body’s natural circuits, Longevity Biotech is developing new treatments through a completely innovative approach, unattainable without the Hybridtide® scaffold.
Longevity Biotech is currently targeting cell surface receptors that have been identified and validated as key disease pathways. Our Hybridtide® molecules are capable of modulating these pathways, resulting in the desired therapeutic outcome. This class of protein-protein interactions (G-Protein Coupled Receptors, GPCRs) is highly complex and challenging, despite several decades of pharmaceutical interest.
Longevity Biotech is pursuing a new and versatile strategy for creating peptide-like molecules that mimic the information content of specific natural prototype peptides but display superior pharmacokinetic properties relative to conventional peptides. Longevity’s proprietary platform technology promises to provide effective therapeutic and diagnostic agents for a wide range of human diseases. Longevity’s current programs are focused in cardiovascular, metabolic and oncological areas; we are open to partnerships in these and other disease areas.
Longevity’s compounds are created via rational combination of alpha-amino acids, the building blocks of proteins, with carefully chosen unnatural building blocks, to generate Hybridtides®. Properly designed Hybridtides® can recapitulate specific recognition surfaces displayed by natural polypeptides but feature higher metabolic and conformational stability than do conventional peptides. The Longevity approach achieves this desirable profile via internal modifications, which minimize off-target binding behavior and ensuing toxicity. The Hybridtide® strategy is therefore distinguished from other peptidomimetic approaches in which stabilizing or modulating units are appended to the molecular exterior, where they can inadvertently engage unintended biomolecular partners.
The molecular principles underlying Hybridtide® technology were developed at the University of Wisconsin – Madison during many years of fundamental research. Recent successes in proof-of-concept studies led to the founding of Longevity Biotech, Inc., for development of clinically useful Hybridtides® that can inhibit deleterious protein-protein interactions or function as long-lasting agonists at receptors that are naturally modulated by polypeptide ligands. The Hybridtide strategy is particularly promising for targets that are not susceptible to traditional small molecule-based medicinal approaches.
The most mature Hybridtide design pathways involve combination of alpha-amino acid residues with beta-amino acid residues, to generate alpha/beta-peptides. High-resolution structural analysis (academic research) reveals that periodic alpha-to-beta substitution can deliver Hybridtides that very closely mimic alpha-helices from natural polypeptides.
Caption: Crystal structure of an alpha/beta-peptide that mimics the Puma BH3 domain, bound to anti-apoptotic protein Bcl-xL (PDB 2YJ1). The alpha/beta-peptide is shown in yellow (alpha residues) and blue (beta residues); Bcl-xL is gray.
Successful mimicry of the CHR domain of HIV protein gp41 shows that this strategy is effective even for very long helices. In this case, the optimized alpha/beta-peptide blocks infection by clinical strains of the virus in cell-based assays, and this compound displays ~300-fold slower degradation by an aggressive protease relative to an analogous conventional peptide (purely alpha residues).
Caption: Crystal structure of an alpha/beta-peptide that mimics the CHR domain of HIV protein gp41, bound to an engineered protein that contains five of the six alpha-helices in the six-helix-bundle form of the gp41 trimer (PDB 3O43). The alpha/beta-peptide is shown in yellow (alpha residues), red and blue (beta residues); the protein partner is gray.
February 21, 2014
Longevity’s Hybridtides not just ‘me-too’ peptides
January 13-15, 2014 – San Francisco
Longevity Biotech will be presenting at the Biotech Showcase 2014 for privately held biotechnology firms on Wednesday January 15th at 9:00am.
January 1, 2014 – Philadelphia
Longevity Biotech has been awarded a Phase I SBIR grant from the NSF to further the oral delivery efforts of Hybridtide-based therapeutics.
October 21, 2013 – Philadelphia
WARF/Longevity Biotech receive notice of allowance for Hybridtide platform patent
June 25th, 2013 – Hawaii
Longevity Biotech Chief Scientific Officer wins 2013 Makineni Award
April 21-24, 2013 – Chicago
Longevity Biotech will be participating in the 2013 Biotechnology Entrepreneurship Boot Camp and partnering activities
February 25, 2013
Longevity: Internal Improvements. Longevity stabilizing peptides internally with non-natural beta amino acids.
January 7-9, 2013 – San Francisco
Longevity Biotech will be presenting at the Biotech Showcase 2013 for privately held biotechnology firms.
December 11, 2012 – online
Longevity Biotech will be participating in this national virtual conference for early stage university spinouts.
November 13-14th, 2012 – Madison, Wisconsin
Wisconsin Investors Forum
October 22, 2012 – Philadelphia, PA
Longevity Biotech will be presenting as part of the Company Showcase program at the PA Biotech 2012 conference.
April 17, 2012 – San Francisco, CA
Tech visionary Thiel sets out to spark a biotech revolution
June 21, 2011 – Philadelphia, PA
Science Center welcomes five early stage companies in lifesci, investment, and medical device
Longevity Biotech is a leading biotech firm working to develop an entirely new class of therapeutic compounds (Hybridtides) while enable the investigation of novel therpeutic mechanisms of action (how the drugs work). The Hybridtide molecular scaffold stablizes biological active molecules from the inside out.William F. DeGrado, Ph.D. Michael R. Rickels, MD James Runo, MD Stephen M. Sammut Peter Schultz, Ph.D. James A. Waschek, Ph.D.
Dr. DeGrado is a prominent researcher working in the area of chemical biology, biochemistry, and biophysics at the University of California, San Francisco medical school. Prior to his current position, he spent 10 years at the University of Pennsylvania and 15 years at DuPont and DuPont-Merck Pharmaceuticals, reaching the level of Senior Director of Medicinal Chemistry before moving to academics in 1996. Dr. DeGrado has earned numerous awards, including membership in the National Academy of Sciences, and the American Association for the Advancement of Science, and he has been an adjunct faculty member at Harvard University and Johns Hopkins Medical Schools. He is a recent President of the Protein Society, has served on the Editorial Boards of 19 scientific journals, and has authored over 200 publications and multiple issued U.S. patents. Dr. DeGrado is the founder of PolyMedix (PYMX.OB) as well as InfluMedix, and has been on the scientific advisory boards for Xencor, Sunesis, and ExSAR. He holds a Ph.D. in Chemistry from the University of Chicago, and B.S. from Kalamazoo College.
Michael R. Rickels, MD, MS received his undergraduate degree from Colgate University, his medical degree and a Master’s degree in Translational Research from the University of Pennsylvania. Dr. Rickels conducts patient-oriented diabetes research that aims at understanding the pathogenesis of different types of diabetes and the in vivo mechanisms of new diabetes treatments. Dr. Rickels’ studies involve methodologies for quantifying insulin secretion, insulin sensitivity, and glucose counterregulatory responses to hypoglycemia, and include the frequently-sampled intravenous glucose tolerance test, the glucose-potentiated arginine test, and hyperinsulinemic euglycemic and hypoglycemic clamps. Present work in Type 1 Diabetes is focused on patients with long-standing disease and is examining the effects of isolated islet or whole pancreas transplantation on insulin secretion and sensitivity, the effects of islet transplantation or real-time continuous glucose monitoring on glucose counterregulatory defenses against hypoglycemia, and the effects of the incretin hormone GLP-1 on insulin secretion in islet and pancreas transplant recipients. Current work in Type 2 Diabetes is focused on understanding early defects in insulin secretion and the impact on early impairments of different strategies for enhancing GLP-1 effects. Additional work is directed at investigating genetic determinants of insulin secretory reserve in humans and on understanding the pathophysiologic defects involved in the etiology of Cystic Fibrosis Related Diabetes. Dr. Rickels’ clinical practice specializes in the diagnosis and treatment of diabetes, hypoglycemia disorders, and general endocrinologic problems. Dr. Rickels predominantly cares for patients with Type 1 and Type 2 Diabetes, and is particularly interested in islet and pancreas transplantation as therapies for Type 1 Diabetes, as well as islet autotransplantation for patients undergoing total pancreatectomy, and serves as Medical Director for the Pancreatic Islet Cell Transplantation program at the Hospital of the University of Pennsylvania.
James Runo, MD received his medical degree in 1997 from Indiana University School of Medicine and went on to Internal Medicine residency at Indiana University School of Medicine finishing in 2000. He then completed a fellowship in Pulmonary & Critical Care Medicine at Vanderbilt University School of Medicine from 2000 – 2004. Since 2004, he has been an Assistant Professor of Medicine at University of Wisconsin School of Medicine and Public Health and attends on the Pulmonary Consultation, Intensive Care Unit, and Advanced Pulmonary Services. Dr. Runo sees patients in the pulmonary clinic for all pulmonary disorders but has established a Pulmonary Hypertension Clinic focusing on this rare and complex disorder. He has published peer reviewed articles on pulmonary hypertension and is involved in clinical trials in pulmonary hypertension.
Steve has a career that is both commercial and academic. Outside of Wharton, Steve is Venture Partner, Burrill & Company, a merchant bank and venture capital fund focused on the life sciences and health care. His role at Burrill & Company is development and general management of overseas venture capital funds, particularly in the Asia-Pacific region and Latin America.
During his 20 years on the Wharton faculty, he has created ten courses that he has taught to nearly 8000 students. These courses include: Health Care Entrepreneurship,
Private Equity in Emerging Markets, and Venture Capital and Entrepreneurial Management.
During his private sector career, Steve has been involved in the creation or funding of nearly 40 biotechnology and information technology companies globally. During his career he has structured and negotiated nearly 20 acquisitions and divestitures and over 100 technology licenses domestically and internationally. He is on numerous Boards of Directors including HealthRight International, the Center for Medicine in the Public Interest, Dynamis Therapeutics, and Combinent BioMedical Systems
Steve previously held the positions of Vice President of Development of Teleflex Incorporated and Vice President, S.R.One, Ltd., GlaxoSmithKline’s venture fund. During his career he was Managing Director of the Center for Technology Transfer at the University of Pennsylvania, and held a similar position at Thomas Jefferson University. At the start of his career, Mr. Sammut co-founded and served as CEO of the Delaware Valley Organ Transplant Program over an eight year period building it into one of the largest organ banks in the world.
Professor Schultz founded and was the Institute Director of the Genomics Institute of the Novartis Research Foundation (GNF) in San Diego, CA from 1999 to 2010. In addition, Dr. Schultz is a founder of Affymax Research Institute, Syrrx, Kalypsys, Phenomix, Symyx Therapeutics, Ilypsa, Ambrx and Wildcat Technologies, pioneers in the application of diversity based approaches to problems in chemistry, materials science and medicine. His awards include the Waterman Award of the National Science Foundation, membership in the National Academy of Sciences and National Institute of Medicine, the 1994 Wolf Prize in Chemistry, the 2003 Paul Ehrlich Prize, and the 2005 Arthur C. Cope Award of the American Chemical Society. Dr. Schultz began his academic career in 1985 as a Professor of Chemistry at Lawrence Berkeley National Laboratory and an Investigator of the Howard Hughes Medical Institute. Professor Schultz has been a faculty member at Scripps since 1999 and has over 400 publications to date.
Dr. Waschek is a Professor of Psychiatry and Biobehavioral Science at the David Geffen School of Medicine at the University of California at Los Angeles (UCLA), and is an expert in the molecular and cellular biology and physiological actions of neuropeptides. Dr. Waschek received a Ph.D. in Pharmaceutical Chemistry in 1984 from the University of California at San Francisco, after which he took a postdoctoral position at the National Institutes of Health (NIH). In 1988 he came to UCLA, where his research has centered on three broad, but related topics: 1) CNS development, degeneration, injury, and repair, 2) neuroinflammatory conditions such as multiple sclerosis, and maternal inflammation-induced perinatal white matter disease, and 3) brain tumor pathogenesis. A past and continuing objective has been to better understand the biological roles of neuropeptides in these processes, especially the two related peptides PACAP and VIP (pituitary adenylyl cyclase activating peptide and vasoactive intestinal peptide, respectively). A major contribution in this area was his discovery first reported in 1998 that PACAP and functional PACAP receptors are highly expressed in the murine neural tube and other germinal centers, and that PACAP acts in part via cAMP and protein kinase A to regulate neural patterning and proliferation via antagonism of hedgehog signaling. Using gene targeting and other approaches, he found this interaction to be relevant not only during brain development, but also in the pathogenesis of malignant pediatric brain tumors. In other work, he has demonstrated growth factor-like actions of PACAP in the maturation of white matter (myelin) and in axon regeneration after injury. Most recently, he determined that VIP and PACAP are critically involved in inflammatory responses after nerve injury and in other pathologies such as lung and liver injury, colitis, cystitis, viral infection, and in an animal model of multiple sclerosis. These studies have revealed significant effects of PACAP and VIP PACAP loss on innate cellular responses to injury, as well as in Th1, Th2, and Th17 differentiation, regulatory T cell production, and immune cell invasion of the CNS parenchyma. Has been continuously funding for his research by the NIH since 1984, and is also currently receiving funding through major grants from the National Multiple Sclerosis Society and the National Brain Tumor Society. Dr. Waschek has served on NIH study sections almost continuously since 2006, and served as an external reviewer for the newly-formed LOWEE Institute on Tumors and Inflammation in Marburg, Germany, and a consultant for the Japanese-Israeli Scientific and Technological Cooperation Agreement in Life Sciences in the Topic of Stem Cell Research
Dr. Shandler brings nearly a decade of commercial and scientific operating experience to Longevity. Prior to founding Longevity, Dr. Shandler worked in venture capital as an associate for the BioAdvance Greenhouse fund. At BioAdvance, Dr. Shandler focused on therapeutics and biomarkers. Prior to BioAdvance, Dr. Shandler worked for Merck Research Labs (MRK) as a portfolio analyst, guiding project prioritization efforts across the neuroscience portfolio. Prior to Merck, Dr. Shandler was a product manager for PolyMedix (PYMX.OB), an early stage biotech company developing antimicrobial and cardiovascular therapeutics. While at PolyMedix, Dr. Shandler assisted with the successful Series A fundraising activities. Dr. Shandler also served as a consultant and subject matter expert in Accenture’s (ACN) Pharmaceutical and Medical Products group, advising leading pharmaceutical and biotechnology companies. Early in his career, he worked for Inventa, a Silicon Valley startup helping craft business solutions for Fortune 500 and startup companies alike. Dr. Shandler received his Ph.D. in biochemistry and molecular biophysics from the University of Pennsylvania as well as an MBA from The Wharton School as a healthcare major. Dr. Shandler holds a B.A. in computer science from Brandeis University and a certificate of bioinformatics from Stanford University.
Dr. Gellman is the Ralph F. Hirschmann Professor of Chemistry at the University of Wisconsin – Madison. Dr. Gellman earned an A.B. from Harvard University, a Ph.D. in chemistry from Columbia University. After post-doctoral research at Caltech, Dr. Gellman joined the UW-Madison faculty in 1987. Dr. Gellman’s research spans the fields of organic, biological and biophysical chemistry. In addition, he has authored more than 200 peer-reviewed papers and is an inventor on more than 15 pending and issued patents. Much of his laboratory’s work focuses on “peptidomimetics”, which are unnatural oligomers that adopt protein-like conformations and include Hybridtides®.
Dr. Gellman’s research has been recognized by the Arthur C. Cope Scholar Award (1997, American Chemical Society), the Vincent du Vigneaud Award (American Peptide Society, 2006) and the Ralph F. Hirschmann Award in Peptide Chemistry (American Chemical Society, 2007). Dr. Gellman has served the scholarly community in a variety of roles, including as a member of the National Institutes of Health Bioorganic and Natural Products Study Section (1999-2002), as Chair of the Peptides Gordon Conference (2010) and as an Editorial Advisory Board member for several leading journals.
Longevity Biotech is happy to consider a variety of partnership structures, including those listed below.
- Hybridtide® license to enable your internal research programs
- Longevity therapeutic co-development
- Research license to investigate the application of our compounds for your therapeutic area of interest
- Longevity Biotech corporate investment
- Co-development partnerships with therapeutically aligned non-profit agencies
- Government agency contracts
- Academic research license
If any of these structures meet your needs, please contact us to learn more.
Hybridtide® Optimization Toolkit™
Longevity Biotech has an optimized process to rapidly apply the Hybridtide® process to new targets. This process typically yields highly stable and highly active leads in less than 50 compounds. While this process is target specific, we are not limited by secondary structure nor sequence space. Our most successful programs have some preliminary Structure Activity Relationship data along with a robust activity assay. Protein or peptide structure is not a requirement.
- Enhancement of α-Helix Mimicry by an α/β-Peptide Foldamer via Incorporation of a Dense Ionic Side-Chain Array.
Johnson LM, Mortenson DE, Yun HG, Horne WS, Ketas TJ, Lu M, Moore JP, Gellman SH. J. Am. Chem. Soc., 2012, 134 (17), pp 7317–7320
- Extending foldamer design beyond α-helix mimicry: α/β-peptide inhibitors of vascular endothelial growth factor signaling.
Haase HS, Peterson-Kaufman KJ, Lan Levengood SK, Checco JW, Murphy WL, Gellman SH. J Am Chem Soc. 2012 May 9;134(18):7652-5.
- Evaluation of diverse α/β-backbone patterns for functional α-helix mimicry: analogues of the Bim BH3 domain.
Boersma MD, Haase HS, Peterson-Kaufman KJ, Lee EF, Clarke OB, Colman PM, Smith BJ, Horne WS, Fairlie WD, Gellman SH. J Am Chem Soc. 2012 Jan 11;134(1):315-23. Epub 2011 Dec 8.
- Structural basis of Bcl-xL recognition by a BH3-mimetic α/β-peptide generated by sequence-based design.
Lee EF, Smith BJ, Horne WS, Mayer KN, Evangelista M, Colman PM, Gellman SH, Fairlie WD. Chembiochem. 2011 Sep 5;12(13):2025-32. doi: 10.1002/cbic.201100314. Epub 2011 Jul 8.
- Broad Distribution of Energetically Important Contacts across an Extended Protein Interface.
Johnson LM, Horne WS, Gellman SH. J. Am. Chem. Soc., 2011, 133 (26), pp 10038–10041
- Structural and biological mimicry of protein surface recognition by α/β-peptide foldamers.
Horne WS, Johnson LM, Ketas TJ, Klasse PJ, Lu M, Moore JP, Gellman SH. Proc Natl Acad Sci U S A. 2009 Sep 1;106(35):14751-6. Epub 2009 Aug 17.
- High-resolution structural characterization of a helical α/β-peptide foldamer bound to the anti-apoptotic protein Bcl-xL.
Lee EF, Sadowsky JD, Smith BJ, Czabotar PE, Peterson-Kaufman KJ, Colman PM, Gellman SH, Fairlie WD. Angew Chem Int Ed Engl. 2009;48(24):4318-22.
- Interplay among side chain sequence, backbone composition, and residue rigidification in polypeptide folding and assembly
Horne WS, Price JL, Gellman SH. PNAS July 8, 2008 vol. 105 no. 27 9151-9156
- Sequence-based design of α/β-peptide foldamers that mimic BH3 domains.
Horne WS, Boersma MD, Windsor MA, Gellman SH. Angew Chem Int Ed Engl. 2008;47(15):2853-6.
- Exploration of backbone space in foldamers containing α- and β-amino acid residues: developing protease-resistant oligomers that bind tightly to the BH3-recognition cleft of Bcl-xL.
Sadowsky JD, Murray JK, Tomita Y, Gellman SH. Chembiochem. 2007 May 25;8(8):903-16.
Current Job Openings @ Longevity Biotech, Inc
Location: Philadelphia, PA – United States
Instructions: Please send resumes and cover letters to Careers@LongevityBiotech.com and include the Job ID number in subject line.
Senior Peptide Biochemist – Job ID #247
- 7+ years bench experience in all aspects of peptide biochemistry
- High profile publication track record highly preferred
- Molecular biology experience highly preferred
Senior Formulation Scientist – Job ID #311
- 7+ years bench experience in formulation of 15+ different compounds
- Bioanalytical experience highly preferred
- In vivo experience highly preferred
Preclinical Development Lead – Job ID #128
- Project lead for 3+ successful IND filings
- Cardiovascular, metabolics and oncology therapeutic areas highly preferred
- FDA / EMEA Regulatory experience highly preferred
Longevity Biotech, Inc. is a leading edge, nimble and entrepreneurial EEO employer committed to a diverse and dynamic workplace with merit based advancement opportunities.
Principals only. No recruiters.
HybridtidesHybridtides® are a new class of therapeutic which incorporate non-natural amino acids. Hybridtides® overcome the challenges of targeting complex protein-protein interfaces for medicinal use. The discreet recognition of these interfaces are crucial in the treatment of many diseases. To date, traditional small molecule approaches have not been able to therapeutically modulate these interfaces due to the extended surface area and complex interactions. The specific non-natural amino acids we use along with the proprietary way in which we use them lead to a dramatic improvement in digestive resistance. The representative data on our targets pages suggest that significantly improved half-lives can be achieved while retaining the necessary biological activity.
Anti-Viral Fusion Inhibitor
Longevity Biotech has licensed a highly effective viral fusion inhibitor Hybridtide® from the University of Wisconsin – Madison. This compound has a vastly superior in-vitro digestive stability when compared to a closely related α-amino acid based fusion inhibitor, while retaining nearly identical activity.
Cardiovascular Disease – Primary Arterial Hypertension (PAH) – Vasoactive Intestinal Peptide
VIP is a highly studied neuropeptide with a variety of function throughout the body. VIP has been implicated as a possible therapeutic mechanism for a number of diseases. The primary function of VIP, when it signals through the VPAC2 receptor, is as a potent vasodilator. In addition, VIP interacts with the immune system as a regulator of the inflammatory response, by upregulating anti-inflammatory cytokines (IL-10 and TGF-β1) while simultaneously down regulating pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1β, and MIP-2). Thus is it no surprise that VIP has also demonstrated beneficial effects in other autoimmune and inflammatory diseases including, chronic obstructive pulmonary disease, arthritis, multiple sclerosis and Parkinsons disease to name a few. Furthermore, as an endocrine system member, VIP has also demonstrated therapeutic benefits in the diabetes world as well, specifically as an anti-hyperglycemic.
Longevity Biotech has identified uniquely selective Hybridtide agonists for the VPAC2 receptor subtype which is responsible for vasodilation as well as anti-inflammatory effects.
Metabolic Syndrome – Dual GLP1 / GIP agonist
The GLP1 mechanism has been well studied for its clinical value in treating Type 2 Diabetes. Recent research however has implicated that a more complex set of interactions can deliver even greater clinical value by dramatically improving on the well-known GLP1 pathway. By developing a novel Hybridtide® candidate that is capable of targeting both GLP1 and GIP simultaneously with a single compound, the delicate balance of activation of these two closely related receptors can be achieved. This pathway, together with the intrinsic benefits of the Hybridtide® molecular scaffold have resulted in a preclinical lead candidate for the treatment of metabolic syndrome, including Type 2 Diabetes. It should be noted that we were able to identify a preclinical lead in significantly less than 50 compounds for this program.
Oncology – Breast Cancer – Vasoactive Intestinal Peptide
When the VPAC1 receptor is blocked (antagonized) in breast cancer cells, this mechanism is capable of reducing the rate of tumor growth. Furthermore, this receptor is highly internalized upon activation and thus capable of effectively delivering a highly targeted dose of chemotherapeutic payload to these cells. Longevity is currently in early preclinical development of therapeutic Hybridtides® for oncology. Contact us to learn more.