Eidos Therapeutics Initiates Phase 2 Clinical Trial for AG10 Targeting Transthyretin Amyloidosis Cardiomyopathy

SAN FRANCISCO, May 3, 2018 /PRNewswire/ — Eidos Therapeutics, Inc., a clinical stage biopharmaceutical company developing a novel oral therapy to treat transthyretin (TTR) amyloidosis (ATTR), today announced dosing of the first patient in the Phase 2 clinical trial of AG10 in patients with ATTR cardiomyopathy (NCT03458130).

The Phase 2 trial will enroll approximately 45 symptomatic ATTR cardiomyopathy patients in a randomized, double-blind, placebo-controlled design. The trial will include a minimum of 30% of patients with mutant ATTR cardiomyopathy, with the remainder having wild type ATTR cardiomyopathy.

Patients will be randomized in a 1:1:1 fashion to placebo or one of two different doses of AG10 on a background of stable heart failure therapy. If all doses are well-tolerated, patients will be treated for 28 days.

“ATTR cardiomyopathy represents a significant unmet need with a poor prognosis and limited existing treatment options, and further, the prevalence of the disease is increasing dramatically with improved awareness and novel, non-invasive diagnostic techniques,” said Rodney Falk, M.D., director of the cardiac amyloidosis program at Brigham and Women’s Hospital and associate professor of medicine at Harvard Medical School. “The preclinical and Phase 1 data describing AG10 indicate that it could be a valuable treatment option for these patients, and I am eager to participate in the trial and learn more about AG10’s potential.”

The primary objective of this trial is to evaluate the safety and tolerability of AG10. The trial will also characterize the pharmacokinetics of AG10 administered twice daily. Finally, the trial will measure and confirm TTR stabilization by validated ex vivo assays, namely fluorescent probe exclusion and immunoblotting. As previous clinical studies have demonstrated that increasing levels of TTR stabilization lead to improved clinical benefit, the trial aims to provide clinical proof of concept to support potential subsequent pivotal trials.

This Phase 2 trial follows the successful completion of a Phase 1 trial of AG10 in healthy volunteers, reported at the 16thInternational Symposium on Amyloidosis in Kumamoto, Japan on March 29, 2018. The Phase 1 trial included single ascending dose, multiple ascending dose (MAD) and food effect components. AG10 was found to be well-tolerated at all doses. No serious adverse events were observed in the trial, vital signs and cardiac safety measures revealed no findings of clinical concern, and liver, kidney and hematological parameters were all within normal limits.

“The positive results of our Phase 1 trial of AG10 in healthy volunteers encouraged our rapid advancement into a Phase 2 trial in patients with ATTR cardiomyopathy,” said Jonathan Fox, M.D., Ph.D., the company’s president and chief medical officer. “Our preclinical and Phase 1 data provide evidence that AG10 could be beneficial for both wild type and mutant ATTR cardiomyopathy patients, and this Phase 2 trial aims to provide additional information in these specific populations.”

Pharmacokinetic measurements demonstrated that AG10 is rapidly and consistently absorbed with a terminal half-life of approximately 25 hours. Ex vivo pharmacodynamic assays demonstrated 100% TTR stabilization at peak plasma concentrations and >95% stabilization on average in the final MAD cohort. TTR stabilization measurements were highly correlated between assays and a clear dose-dependency of stabilization was observed.

“Based on genetic evidence and previous clinical trials, we believe that increasing levels of TTR stabilization lead to increased clinical benefit,” said Uma Sinha, Ph.D., the company’s chief scientific officer. “The ex vivo measurements used in our Phase 1 trial demonstrate that AG10 potently binds TTR tetramers and prevents their dissociation into monomers, which is thought to be the rate limiting step in ATTR pathogenesis. These data support our belief that AG10 could become a best-in-class TTR stabilizer treatment for ATTR patients.”

The company expects to report topline results from this Phase 2 trial by the end of 2018. Eidos expects to launch a second Phase 2 trial in patients with ATTR polyneuropathy later this year.

About AG10

AG10 is an orally-administered, small molecule designed to potently stabilize tetrameric TTR, thereby halting at its outset the series of molecular events that give rise to ATTR. Eidos’ approach, based on over 25 years of research, mimics a naturally-occurring genetic rescue mutation that protects high-risk individuals from developing ATTR by stabilizing the TTR tetramer. In fact, the binding of AG10 to tetrameric TTR creates strong molecular bonds at the same locations as the rescue mutation known as T119M, which “super-stabilizes” TTR and has been shown to enhance survival. This specific binding mode underlies AG10’s ability at peak blood concentrations to completely stabilize tetrameric TTR and prevent its dissociation into disease-causing TTR monomers in the bloodstream. Based on data from previous clinical trials in ATTR demonstrating that preventing the generation of TTR monomers from circulating in the bloodstream leads to improved clinical outcomes, Eidos believes that AG10 could be a best-in-class therapy.

About transthyretin amyloidosis (ATTR)

ATTR represents a significant unmet need, with a comparatively large patient population in the context of rare genetic diseases and an inadequate current standard of care. There are three distinct diseases that comprise the ATTR family: wild-type ATTR cardiomyopathy (ATTRwt-CM), mutant ATTR cardiomyopathy (ATTRm-CM), and ATTR polyneuropathy (ATTR-PN). The worldwide prevalence of each disease is approximately 200,000 patients, 40,000 patients and 10,000 patients, respectively, although Eidos believes the cardiomyopathic forms of the disease are significantly underdiagnosed due to non-specific symptoms and a historical reliance on an invasive heart biopsy for diagnosis. Eidos believes that improving

disease awareness and the introduction of a non-invasive, imaging-based diagnostic scan, coupled with appropriate blood tests, are significantly increasing rates of diagnosis for ATTRwt-CM and ATTRm-CM.

All three forms of ATTR are progressive and fatal, and no disease-modifying therapies have been approved by the FDA. For patients with ATTRwt-CM and ATTRm-CM, symptoms usually manifest later in life (age 50+), with median survival of three to five years from diagnosis. ATTR-PN either presents in a patient’s early 30s or later (age 50+), and results in a median life expectancy of five to ten years from diagnosis. Progression of all forms of ATTR causes significant morbidity, impacts productivity and quality of life, and creates a significant economic burden due to the costs associated with progressively greater patient needs for supportive care.

About Eidos Therapeutics

Eidos is a clinical stage biopharmaceutical company focused on addressing the large and growing unmet need in diseases caused by transthyretin (TTR) amyloidosis (ATTR). Eidos seeks to treat this well-defined family of diseases at their collective source by stabilizing TTR, a therapeutic approach that is supported by genetic evidence as well as previous clinical trials. The company’s product candidate, AG10, is an orally-administered small molecule designed to potently stabilize TTR, suggesting a best-in-class treatment with the potential to halt the progression of ATTR. The development of AG10 is led by a proven management team who are responsible for developing over 30 molecules through IND applications and more than 10 approved drugs. Together with patients and physicians, Eidos aims to bring a safe, effective and disease-modifying treatment for ATTR to market as quickly as possible.

Eidos Therapeutics Completes $64M Series B Financing

SAN FRANCISCO, April 5, 2018 /PRNewswire/ — Eidos Therapeutics, Inc., a clinical stage biopharmaceutical company developing a novel oral therapy to treat transthyretin (TTR) amyloidosis (ATTR), today announced a $64.0 million Series B financing. Proceeds from the financing will be used to advance Eidos’ small molecule product candidate, AG10, into Phase 2 clinical trials and to continue preparations for Phase 3 clinical trials. AG10 targets ATTR at its source by potently binding and stabilizing TTR tetramers, the destabilization of which underlies the development of ATTR.

The financing was led by RA Capital Management and included Eidos’ parent company, BridgeBio Pharma, in addition to new investors Janus Henderson, Viking Global Investors, Aisling Capital, Perceptive Advisors, Cormorant Asset Management and Amzak Health Investors. The Series B financing brings the total capital raised by Eidos to approximately $91.0 million.

“Our clinical data demonstrate that AG10 has a safe, well-tolerated profile and is able to stabilize 100% of plasma TTR at peak concentrations and provide average levels of stabilization greater than 95% at steady-state,” said Neil Kumar, PhD, chief executive officer of Eidos. “Given that increasing levels of stabilization have yielded progressively better clinical results in past trials, our near-complete levels of stabilization suggest that AG10 could be a best-in-class solution. We are targeting ATTR at its source by stabilizing TTR, an approach that is validated by genetics and clinical data.”

In connection with the financing, both Rajeev Shah, managing director and portfolio manager at RA Capital, and Eric Aguiar, MD, partner at Aisling Capital, will join Neil Kumar and Hoyoung Huh, MD, PhD, on Eidos’ board of directors.

“ATTR diseases are a large and growing unmet need, and together, they represent one of the largest genetically-defined diseases with inadequate standard of care,” said Rajeev Shah. “We look forward to working with Eidos’ proven management team to bring a disease-modifying treatment for ATTR to market as quickly as possible.”

About AG10

AG10 is an orally-administered, small molecule designed to potently and selectively stabilize tetrameric TTR, thereby halting at its outset the series of molecular events that give rise to ATTR. Eidos’ approach, based on over 25 years of research, mimics a naturally-occurring genetic rescue mutation that protects high-risk individuals from developing ATTR by stabilizing the TTR tetramer. In fact, the binding of AG10 to tetrameric TTR creates strong molecular bonds at the same locations as the rescue mutation known as T119M, which “super-stabilizes” TTR and has been shown to enhance survival. This specific binding mode underlies AG10’s ability at peak blood concentrations to completely stabilize tetrameric TTR and prevent its dissociation into disease-causing TTR monomers in the bloodstream. Given that previous clinical trials in ATTR demonstrate that preventing the generation of TTR monomers from circulating in the bloodstream leads to improved clinical outcomes, Eidos believes that AG10 could be a

best-in-class therapy.

About transthyretin amyloidosis (ATTR)

ATTR represents a significant unmet need, with a comparatively large patient population in the context of rare genetic diseases and an inadequate current standard of care. There are three distinct diseases that comprise the ATTR family: wild-type ATTR cardiomyopathy (ATTRwt-CM), mutant ATTR cardiomyopathy (ATTRm-CM), and ATTR polyneuropathy (ATTR-PN). The worldwide prevalence of each disease is approximately 200,000 patients, 40,000 patients and 10,000 patients, respectively, although the cardiomyopathic forms of the disease are thought to be significantly underdiagnosed due to non-specific symptoms and a historical reliance on heart biopsy to make the diagnosis. Eidos believes that improving disease awareness and the introduction of a non-invasive, imaging-based diagnostic scan, coupled with appropriate blood tests, are significantly increasing rates of diagnosis for ATTRwt-CM and ATTRm-CM.

All three forms of ATTR are progressive and fatal, and no disease-modifying therapies have been approved by the FDA. For patients with ATTRwt-CM and ATTRm-CM, symptoms usually manifest later in life (age 50+), with median survival of 3-5 years from diagnosis. ATTR-PN either presents in a patient’s early 30s or later (age 50+), and results in a median life expectancy of 5-10 years from diagnosis. Progression of all forms of ATTR causes significant morbidity, impacts productivity and quality of life, and creates a significant economic burden due to the costs associated with progressively greater patient needs for supportive care.

About Eidos Therapeutics

Eidos is a clinical stage biopharmaceutical company focused on addressing the large and growing unmet need in diseases caused by transthyretin (TTR) amyloidosis (ATTR). Eidos seeks to treat this well-defined family of diseases at their collective source by stabilizing TTR, a therapeutic approach that is supported by genetic evidence as well as previous clinical trials. The company’s product candidate, AG10, is an orally-administered small molecule designed to potently stabilize TTR, suggesting a best-in-class treatment with the potential to halt the progression of ATTR. The development of AG10 is led by a proven management team who are responsible for developing over 30 molecules through IND applications and more than 10 marketed drugs. Together with patients and physicians, Eidos aims to bring a safe, effective and disease-modifying treatment for ATTR to
market as quickly as possible.

Eidos Therapeutics to Host Symposium on TTR Stabilization at the 16th International Symposium on Amyloidosis

SAN FRANCISCO, March 20, 2018 /PRNewswire/ — Eidos Therapeutics, a clinical stage biopharmaceutical company developing AG10, a novel precision medicine for transthyretin (TTR) amyloidosis (ATTR), today announced that it will host a symposium regarding TTR stabilization at the 16th International Symposium on Amyloidosis in Kumamoto, Japan, on Thursday, March 29 from 7:40-8:40am (JST).

The symposium is titled “TTR Stabilization for ATTR: Past, Present, and Future” and will be chaired by Dr. Mathew Maurer, from Columbia University. The symposium will feature amyloidosis experts including:

  • Dr. Pablo Garcia-Pavia, Hospital Universitario Puerta de Hierro Majadahonda
  • Dr. Morie Gertz, Mayo Clinic
  • Dr. Julian Gillmore, University College London
  • Dr. Stephen Heitner, Oregon Health Sciences University
  • Dr. Daniel Judge, Medical University of South Carolina
  • Dr. Jose Nativi-Nicolau, University of Utah.

“This symposium brings together some of the greatest leaders in the field to discuss the role of TTR stabilizers in treating ATTR,” said Dr. Jonathan Fox, president and chief medical officer of Eidos. “As we advance our potentially best-in-class TTR stabilizer, AG10, into Phase 2 clinical trials, we will continue working closely with clinical experts and investigators, caregivers, and patients to make new treatments for TTR amyloidosis a reality.”

About AG10

AG10 is a small molecule that selectively and potently binds to and stabilizes the tetrameric transthyretin protein, preventing its dissociation into disease-causing monomers. AG10 has a unique mode of binding that mimics a naturally-occurring, disease-protective mutation. AG10 was discovered by Eidos’ co-founders Isabella Graef, MD and Mamoun Alhamadsheh, PhD, at Stanford University and the University of the Pacific, respectively.

About transthyretin amyloidosis

Transthyretin (TTR) amyloidosis is a progressive, fatal disease caused by the accumulation of misfolded TTR in multiple organ systems. Mutations in TTR destabilize the protein and predispose individuals to developing TTR amyloidosis, though the disease can also develop in older individuals without genetic mutations. Misfolded TTR is toxic to cells, and aggregated amyloid fibers can cause further organ dysfunction.

Over 250,000 people worldwide suffer from TTR amyloidosis, though the patient population may be underestimated due to its rarity and confusion with more common diseases such as heart failure. There are no FDA-approved medications indicated for the treatment of TTR amyloidosis.

About Eidos Therapeutics

Eidos Therapeutics is a clinical stage biopharmaceutical company based in San Francisco. Eidos is singularly focused on addressing the large and growing unmet need in transthyretin amyloidosis with AG10, a small molecule precision medicine that targets the disease at its source by stabilizing tetrameric transthyretin. Launched in 2016 and based on research at Stanford University, Eidos is led by a team of veteran biotechnology executives. Together with patients and physicians, the company aims to bring a safe, effective treatment to market as quickly as possible.

BridgeBio Pharma Licenses Late-Stage Oncology Drug Infigratinib to Tackle FGFR-Driven Maladies; Establishes New Subsidiary QED Therapeutics with $65 Million in Initial Financing

PALO ALTO, Calif., Jan. 30, 2018 /PRNewswire/ — BridgeBio Pharma today announced that it is has licensed infigratinib (BGJ398), a highly potent and selective inhibitor of the tyrosine kinase receptor FGFR, from Novartis. In addition, BridgeBio announced that it was launching new subsidiary QED Therapeutics to drive development of infigratinib with an initial financial commitment of $65 million.

FGFR has been implicated as a driver mutation across multiple oncologies – including roughly one out of every five cases of cholangiocarcinoma and urothelial carcinoma – and in multiple forms of pediatric skeletal dysplasias, namely achondroplasia, which affects one out of every 20,000 live births.

Infigratinib is currently in a Phase 2 clinical trial for patients with chemotherapy-refractory bile duct cancer (cholangiocarcinoma) containing FGFR2 fusions. Early clinical results, recently published in the Journal of Clinical Oncology, demonstrated that the compound showed meaningful activity in this population. 

“We are committed to moving this compound forward in late-stage development and further proving the strong efficacy in cancer that has already been demonstrated across multiple trials,” said Daniel Hoth, M.D., QED’s chief medical officer, who has devoted over three decades to drug development, including time as chief of the Investigational Drug Branch of the National Cancer Institute (NCI).

Cholangiocarcinoma affects approximately 6,000 to 8,000 patients a year in the United States. Treatment options are limited, and survival rates vary depending on whether cholangiocarcinoma is found on the bile duct branches within the liver versus those outside of the liver.

“Despite immense strides in studying potential drugs in cholangiocarcinoma, there remains significant need to provide options to these patients,” said Stacie Lindsey, president of the Cholangiocarcinoma Foundation. “The patients and caregivers we work with are very hopeful given data already generated with infigratinib, and we are excited that the passionate team at BridgeBio and QED are working to advance this drug.”

BridgeBio co-founder and investor Frank McCormick, Ph.D., head of the NCI’s Ras initiative and former CSO and co-founder of Onyx Pharmaceuticals, remarked “Infigratinib embodies the crux of what we set out to do at BridgeBio: develop targeted therapies for genetically-driven tumors and monogenic disorders.”

In addition to its clinical data in FGFR-driven cancer, infigratinib has demonstrated potential in skeletal dysplasias, including achondroplasia. In the early work published in the Journal of Clinical Investigation, researchers demonstrated that low doses of infigratinib corrected pathological hallmarks of achondroplasia in mouse models.

Neil Kumar, Ph.D., chief executive officer of BridgeBio, noted that with infigratinib, “We have a late-stage, targeted oncology compound that has demonstrated clear efficacy in the clinic. With the same molecule, we have a potential best-in-class therapy to treat achondroplasia at its source.”

While specific terms of the deal have not been disclosed, BridgeBio has committed $65 million in financing to QED, which is inclusive of a substantial upfront payment to Novartis as well as equity in QED. Novartis will also receive additional payments upon the realization of development and sales milestones as well as royalties.

About BridgeBio Pharma
BridgeBio is a clinical-stage biotech company developing novel, genetically targeted therapies to improve the lives of patients. The BridgeBio approach combines a traditional focus on drug development with a unique corporate model, allowing rapid translation of early stage science into medicines that treat disease at its source. Founded in 2015 by a team of industry veterans, the company has built a robust portfolio of fifteen transformative assets, each housed in its own subsidiary, ranging from pre-clinical to late stage development in multiple therapeutic areas including oncology, cardiology, neurology, dermatology and endocrinology. The company’s focus on scientific excellence and rapid execution aims to translate today’s discoveries into tomorrow’s medicines.

About QED Therapeutics 
QED Therapeutics, a subsidiary of BridgeBio Pharma, is a biotechnology company focused on precision medicine for FGFR-driven disorders. Our lead candidate is infigratinib, a best-in-class FGFR kinase inhibitor that has shown meaningful clinical activity in chemotherapy-refractory cholangiocarcinoma with FGFR2 fusions. QED is also evaluating infigratinib in preclinical studies for the treatment of achondroplasia. We plan to develop infigratinib in additional FGFR-driven tumor types and rare disorders.


BridgeBio Pharma Appoints Sanuj Ravindran, M.D., and Eric Michael David, M.D. as CEOs-in-Residence to Lead Dermatology and Gene Therapy Programs

PALO ALTO, Calif., Jan. 4, 2018 /PRNewswire/ — BridgeBio Pharma, a clinical-stage biopharmaceutical company, today announced that it has strengthened its executive leadership team with two key hires who will join the company as CEOs-in-residence. Sanuj Ravindran, M.D., will serve as CEO of PellePharm, Inc. and will focus on dermatological and international programs across the BridgeBio portfolio. Eric Michael David, M.D., J.D., joins BridgeBio to lead the company’s gene therapy efforts including two unannounced companies. The new hires join current CEO-in-residence, Shafique Virani, M.D., who is focused on central nervous system and oncology development programs.

“Both Dr. Ravindran and Dr. David are accomplished clinicians and biotechnology industry veterans who share a commitment to BridgeBio’s goal of developing new treatments for patients who have few existing therapeutic options,” said Neil Kumar, PhD, CEO of BridgeBio Pharma.

Sanuj Ravindran was previously chief business officer of aTyr Pharma. Prior to aTyr Pharma, Dr. Ravindran was senior vice president of corporate development at The Medicines Company. Dr. Ravindran completed a residency in internal medicine at Thomas Jefferson University Hospital, received his MD from Jefferson Medical College, his MBA from the Kellogg School of Management, and his BA from Northwestern University.

Eric Michael David is a co-founder of Organovo, where he most recently served as chief strategy officer and executive vice president of preclinical development. Prior to Organovo, Dr. David was an associate principal at McKinsey & Co. Dr. David received his clinical training in internal medicine at New York Presbyterian Hospital / Weill Cornell, his MD from Columbia University College of Physicians and Surgeons, his JD from Columbia Law School and his BA in physics and fine arts from Amherst College.

BridgeBio also announced the promotion of Michael Henderson, M.D., to senior vice president of asset acquisition, operations and strategy and Cameron Turtle, DPhil, to senior vice president of portfolio management and corporate development.

About BridgeBio Pharma

BridgeBio is a clinical-stage biotech company developing novel, genetically targeted therapies to improve the lives of patients. The BridgeBio approach combines a traditional focus on drug development with a unique corporate model, allowing rapid translation of early stage science into medicines that treat rare diseases at its source.

Founded in 2015 by a team of industry veterans, BridgeBio has built a robust portfolio of fifteen transformative drug programs that address genetic diseases across oncology, cardiology, dermatology, neurology, and endocrinology. The drugs are in various phases of development, from pre-clinical to late-stage.

With a commitment to scientific excellence and rapid execution, BridgeBio aims to translate today’s discoveries into tomorrow’s medicines.

PellePharm Appoints Sanuj K. Ravindran, M.D., as President and Chief Executive Officer

MENLO PARK, Calif.–(BUSINESS WIRE)–PellePharm, a clinical-stage biopharmaceutical company committed to targeting rare genetic dermatological conditions at the source, today announced the appointment of Sanuj K. Ravindran, M.D., to the position of president and chief executive officer. In parallel, Dr. Ravindran will join BridgeBio Pharma, PellePharm’s lead investor, as CEO-in-Residence, to advance its broader orphan dermatology portfolio.

“Dr. Ravindran’s biopharma industry experience and rare disease expertise will offer enormous strategic benefit to PellePharm as we move into our next stage of development,” said Ervin Epstein, M.D., chief medical officer and co-founder of PellePharm. “Having been successful with the management and growth of multiple biopharma companies, Dr. Ravindran brings the right experience to PellePharm so that we may offer topical patidegib to patients as swiftly as possible.”

Dr. Ravindran brings more than 15 years of strategic and operational biopharma experience to PellePharm. Most recently, he was chief business officer at aTyr Pharma (“LIFE”), a clinical stage rare disease-focused biotechnology company, where he led corporate and financial strategy, business development, and investor relations. Prior to that, Dr. Ravindran was senior vice president of corporate development for The Medicines Company (“MDCO”), where he worked to execute multiple transactions totaling more than $2 billion in potential aggregate value. Previously a practicing physician, Dr. Ravindran began his industry career as a venture capitalist for 10 years with Burrill & Company, Radius Ventures, and Asian Healthcare Fund. Dr. Ravindran is trained in Internal Medicine and completed his residency training at Thomas Jefferson University Hospital. Dr. Ravindran received his B.A. from Northwestern University, his M.D. from Jefferson Medical College and his MBA from the Kellogg School of Management.

“I am thrilled to join PellePharm at such an important juncture, as the Company prepares to advance topical patidegib one step closer to patients with Gorlin Syndrome. With PellePharm’s scientific premise, clinical progress, and recently strengthened leadership team, the company is well on its way to meeting its mission of delivering therapies for rare genetic dermatological conditions,” said Dr. Ravindran.

PellePharm today also announced that it has expanded its executive team to enhance regulatory and operational capabilities. Alix Alderman is now vice president of regulatory affairs at PellePharm, and Gerd Kochendoerfer, Ph.D., is vice president of technical operations and program management. Both Ms. Alderman and Dr. Kochendoerfer bring many years of experience in drug development, quality management and global regulatory affairs.

“We are pleased to welcome Dr. Ravindran, Dr. Kochendoerfer and Ms. Alderman,” said Neil Kumar, CEO and co-founder of BridgeBio Pharma. “At this inflection point, having the right team in place, with the collective experience this group brings, enables PellePharm to more ably achieve its goal of helping patients with serious unmet dermatologic conditions.”

About Patidegib

Topical patidegib gel has shown early promise in a Phase 2 clinical study in Gorlin Syndrome by blocking the disease at its source within the hedgehog signaling pathway. Topical patidegib was developed to provide the efficacy previously demonstrated by oral patidegib in Phase 1 trials, but without the adverse systemic side effects of oral hedgehog inhibitors. Patidegib’s gel formulation is stable at room temperature for at least two years, making it a viable potential therapy for ongoing, at-home management of Gorlin Syndrome. Topical patidegib currently is being studied in a United States-based Phase 2 clinical trial for the treatment of sporadic basal cell carcinomas (BCCs).

About Gorlin Syndrome

Gorlin Syndrome is a rare, genetic disease characterized by mutations in the tumor suppressor gene encoding Patched1 (PTCH1), which acts as the primary inhibitor of the hedgehog signaling pathway. This leads to hundreds of basal cell carcinomas, especially on the face and sun-exposed areas.

With no FDA-approved drugs available for Gorlin Syndrome, also known as Basal Cell Carcinoma Nevus Syndrome (BCCNS), the standard of care is surgery. People with severe Gorlin Syndrome may have as many as 30 surgeries per year, which can be repetitive and scarring. Approximately 10,000 people in the United States, or one in 31,000, are believed to be affected by Gorlin Syndrome. Gorlin Syndrome is known by several names, including BCCNS, Gorlin-Goltz Syndrome, Basal Cell Nevus Syndrome, or Nevoid Basal Cell Carcinoma Syndrome.

About PellePharm

Founded by world leaders in hedgehog signaling, PellePharm, a BridgeBio company, is committed to targeting rare genetic dermatological conditions, including Gorlin Syndrome and BCCs at the source. PellePharm is committed to improving the quality of life for those suffering from Gorlin Syndrome and BCCs by providing an easy-to-use topical solution that eliminates the need for regular, painful surgeries. Topical patidegib is a first-in-class topical gel formulation of a proprietary hedgehog inhibitor.

About BridgeBio Pharma

BridgeBio is a clinical-stage biotech company developing novel, genetically targeted therapies to improve the lives of patients. The BridgeBio approach combines a traditional focus on drug development with a unique corporate model, allowing rapid translation of early stage science into medicines that treat disease at its source. Founded in 2015 by a team of industry veterans, the company has built a robust portfolio of ten transformative drugs ranging from pre-clinical to late stage development in multiple therapeutic areas including oncology, cardiology, dermatology and endocrinology. The company’s focus on scientific excellence and rapid execution aims to translate today’s discoveries into tomorrow’s medicines.

Contacts

Pure Communications
Katie Engleman, 910-509-3977
kengleman@w2ogroup.com

FDA Grants Breakthrough Therapy Designation and Orphan Drug Designation to PellePharm for Topical Patidegib in Gorlin Syndrome

MENLO PARK, Calif.–(BUSINESS WIRE)–PellePharm, a clinical-stage biopharmaceutical company committed to targeting rare genetic dermatological conditions at the source, today announced that the U.S. Food and Drug Administration (FDA) has granted both Breakthrough Therapy Designation and Orphan Drug Designation to topical patidegib for reduction of the life-long serious clinical morbidity and disease burden of persistently developing basal cell carcinomas (BCCs) in patients with Basal Cell Carcinoma Nevus Syndrome (BCCNS), a rare genetic disease also known as Gorlin Syndrome.

“These two significant FDA designations mark important steps forward in our development of topical patidegib as a drug with substantial potential to reduce the BCC tumor burden in Gorlin Syndrome patients. From our co-discovery of the underlying genetic defect, through over two decades of preclinical research with hedgehog inhibitors, and our recent clinical trials, our team at PellePharm is deeply committed to delivering a safe and effective therapy for people living with Gorlin Syndrome,” said Ervin Epstein, MD, cofounder and chief medical officer of PellePharm. “We are eager to continue our development program and work closely with the FDA and other regulatory authorities to deliver this potential first-in-class therapy to patients as quickly as possible.”

The FDA granted PellePharm Breakthrough Therapy Designation based on results from its Phase 2 trial assessing the safety and efficacy of topical patidegib in patients with Gorlin Syndrome. Topline data from this study were announced in July 2017. Breakthrough Therapy Designation is designed to expedite the development and review of drugs that are intended to treat a serious condition, where preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy.

The FDA granted Orphan Drug Designation based on the relatively low prevalence of Gorlin Syndrome. The FDA’s Orphan Drug Designation program is designed to incentivize and facilitate the development of drugs for rare diseases that affect fewer than 200,000 people in the U.S. Approximately 10,000 people in the United States, or one in 31,000, are believed to be affected by Gorlin Syndrome.

“We are pleased that the FDA recognizes the importance of accelerating the development of topical patidegib for people affected by BCCNS (Gorlin Syndrome),” said Jean Pickford, executive director of the Basal Cell Carcinoma Nevus Syndrome Life Support Network. “People living with BCCNS need additional therapeutic options to help lessen the burden of disease.”

Currently, there are no FDA-approved therapies for Gorlin Syndrome, and the standard of care for this rare disease is surgery. Patients with severe disease have as many as 30 surgeries per year.

PellePharm intends to initiate a Phase 3 clinical trial for patidegib in Gorlin Syndrome in 2018.

About Patidegib

Topical patidegib gel has shown early promise in a Phase 2 clinical study in Gorlin Syndrome by blocking the disease at its source within the hedgehog signaling pathway. Topical patidegib was developed to provide the efficacy previously demonstrated by oral patidegib in Phase 1 trials, but without the adverse systemic side effects of oral hedgehog inhibitors. Patidegib’s gel formulation is stable at room temperature for at least two years, making it a viable potential therapy for ongoing, at-home management of Gorlin Syndrome.

Topical patidegib currently is being studied in a United States-based Phase 2 clinical trial for the treatment of sporadic BCCs.

About Gorlin Syndrome

Gorlin Syndrome is a rare, genetic disease characterized by mutations in the tumor suppressor gene encoding Patched1 (PTCH1), which acts as the primary inhibitor of the hedgehog signaling pathway. This leads to hundreds of basal cell carcinomas, especially on the face and sun-exposed areas.

With no FDA-approved drugs available for Gorlin Syndrome, also known as Basal Cell Carcinoma Nevus Syndrome (BCCNS), the standard of care is surgery. People with severe Gorlin Syndrome may have as many as 30 surgeries per year, which can be repetitive and scarring. Approximately 10,000 people in the United States, or one in 31,000, are believed to be affected by Gorlin Syndrome. Gorlin Syndrome is known by several names, including BCCNS, Gorlin-Goltz Syndrome, Basal Cell Nevus Syndrome, or Nevoid Basal Cell Carcinoma Syndrome.

About PellePharm

Founded by world leaders in hedgehog signaling, PellePharm, a BridgeBio company, is committed to targeting rare genetic dermatological conditions, including Gorlin Syndrome and Basal Cell Carcinomas (BCCs), at the source. PellePharm is committed to improving the quality of life for those suffering from Gorlin Syndrome and BCCs by providing an easy-to-use topical solution that eliminates the need for regular, painful surgeries. Topical patidegib is a first-in-class topical gel formulation of a proprietary hedgehog inhibitor.

About BridgeBio Pharma

BridgeBio is a clinical-stage biotech company developing novel, genetically targeted therapies to improve the lives of patients. The BridgeBio approach combines a traditional focus on drug development with a unique corporate model, allowing rapid translation of early stage science into medicines that treat disease at its source. Founded in 2015 by a team of industry veterans, the company has built a robust portfolio of ten transformative drugs ranging from pre-clinical to late stage development in multiple therapeutic areas including oncology, cardiology, dermatology and endocrinology. The company’s focus on scientific excellence and rapid execution aims to translate today’s discoveries into tomorrow’s medicines.

Contacts

Pure Communications
Kelly Lindenboom, 617-763-7281
klindenboom@purecommunications.com

Preclinical Data Demonstrates Potential of Eidos Therapeutics’ Lead Compound for the Treatment for Transythyretin Amyloidosis

Data presented at AHA 2017 Scientific Sessions

PALO ALTO, Calif., Nov. 15, 2017 /PRNewswire/ — Eidos Therapeutics, a subsidiary of BridgeBio Pharma, today announced that recently presented preclinical data highlight the potential of AG10 to treat TTR amyloid cardiomyopathy (ATTR-CM). These data were shared publicly for the first time yesterday as oral podium presentations at the American Heart Association’s (AHA) 2017 Annual Scientific Sessions in Anaheim, CA. Eidos has recently initiated clinical trials to evaluate the potential of AG10 in treating this progressive, fatal disease.

ATTR-CM is a progressive, fatal disease caused by the accumulation of misfolded ATTR fibrils in the heart. Transthyretin (TTR) typically exists as a tetramer in the serum. With certain mutations, the four-part molecule can destabilize and dissociate into individual monomers. The monomers are unstable and can misfold and aggregate as amyloid fibrils. These deposits are toxic to cardiac muscle cells and limit the heart’s ability to fill completely during relaxation, leading to progressive and fatal heart failure.

Data from Eidos’ in vitro and animal studies of AG10 were presented in a rapid-fire oral session by Uma Sinha, Ph.D., Eidos’ chief scientific officer. These experiments demonstrated that AG10 binds native, tetrameric TTR in human and animal serum and prevents its dissociation into disease- causing monomers. Dr. Sinha also presented a preclinical pharmacokinetic evaluation of AG10 that suggests the potential for once daily oral dosing in ATTR patients.

Additionally, in a full oral presentation, Isabella Graef, Eidos’ co-founder and assistant professor of pathology at Stanford University, described biochemical experiments that demonstrated the ability of AG10 to stabilize a series of mutant proteins associated with TTR-CM.

“Taken together, these nonclinical studies clearly demonstrate the potential for AG10 to be orally dosed in patients once daily and result in blood levels of AG10 that completely stabilize the native tetrameric form of TTR,” said Dr. Sinha. “It is well recognized that dissociation of TTR tetramers into monomers is the initial step in the development of ATTR, and that the stability of TTR tetramers is reduced by the disease-promoting mutations examined in Eidos’ studies. By stabilizing TTR tetramers in the blood, AG10 targets ATTR at its source and offers the potential to slow or halt progression of disease.”

About AG10

AG10 is a small molecule that selectively and potently binds to and stabilizes the tetrameric protein transthyretin, preventing its dissociation into disease-causing monomers. AG10 was discovered and initially developed by Eidos’ co-founders Isabella Graef, MD, and Mamoun Alhamadsheh, PhD, at Stanford University and the University of the Pacific, respectively.

About transthyretin amyloid cardiomyopathy (ATTR-CM)

ATTR-CM is a progressive, fatal disease caused by the accumulation of misfolded ATTR fibrils in the heart. These deposits are toxic to cardiac muscle cells and limit the heart’s ability to fill completely during relaxation, leading to progressive and fatal heart failure.

Approximately 240,000 people worldwide suffer from ATTR cardiomyopathy, though the patient population may be underestimated due to its rarity and confusion with more common forms of heart failure. Most patients are diagnosed after age 60, when the disease is already advanced, and may progress rapidly.

Some patients are predisposed to ATTR cardiomyopathy due to mutations in the gene that encodes TTR. The most prevalent pathogenic mutation, V122I TTR, is carried by 3.4% of African Americans.

There are no FDA-approved medications indicated for the treatment of ATTR cardiomyopathy.

About Eidos Therapeutics

Eidos Therapeutics is a clinical stage biopharmaceutical company based in the San Francisco Bay Area. Eidos is developing AG10 as a targeted therapeutic for transthyretin amyloidosis. The company’s singular mission is to improve the lives of patients suffering from this disease. Launched in 2016 after years of research supported by Stanford’s TRAM and SPARK programs, Eidos is led by a team of veteran biotechnology executives.

Together with patients and physicians, the company aims to bring a safe, effective treatment to market as quickly as possible.

About BridgeBio Pharma

BridgeBio is a clinical-stage biotechnology company developing novel, genetically targeted therapies to improve the lives of patients. The BridgeBio approach combines a traditional focus on drug development with a unique corporate model, allowing rapid translation of early stage science into medicines that treat rare diseases at their source.

Founded in 2015 by a team of industry veterans who previously brought more than a dozen products to market, BridgeBio has built a portfolio of ten transformative drug programs that address rare diseases across oncology, cardiology, dermatology and endocrinology. The drugs are in various phases of development, from discovery to late clinical stage.

With a commitment to scientific excellence and rapid execution, BridgeBio aims to translate today’s discoveries into tomorrow’s medicines.