Impel Neuropharma Announces Positive Phase 1 Trial For INP105 For The Treatment Of Acute Agitation In Bipolar I Disorder And Schizophrenia

Study Showed a Safety and Tolerability Profile Consistent with Currently Marketed Formulations of Olanzapine

Data Demonstrated Nasal Delivery of INP105 (POD-olanzapine) Achieved Peak Olanzapine Plasma Levels Twice as Fast as Intramuscular Injection, Ten-Times Faster than Orally-Disintegrating Tablets

SEATTLE, Jan. 6, 2019 /PRNewswire/ — Impel NeuroPharma, a Seattle-based, privately-held biopharmaceutical company focused on innovative therapies for the treatment of central nervous system (CNS) disorders, today announced positive results of a Phase 1 trial of INP105. INP105 is a drug-device combination which delivers an optimized formulation of olanzapine, the current gold standard of treatment for acute agitation, via Impel’s proprietary Precision Olfactory Delivery, or POD®, nasal delivery device. INP105 is being studied for the treatment of acute agitation in bipolar I disorder and schizophrenia.

Results demonstrated that INP105 reached peak plasma levels (Tmax) twice as fast as intramuscular olanzapine (Zyprexa®), and ten-times faster than orally-disintegrating tablets (ODT, Zyprexa Zydis®). Maximum and total plasma levels (Cmax and AUC) were similar to intramuscular delivery and exceeded the total plasma levels for ODT. Pharmacodynamic measures of sedation, including Visual Analogue Scale (VAS), the Agitation and Calmness Evaluation Scale (ACES) and Digit Symbol Substitution Test (DSST) all showed a robust statistical significance compared to placebo.

“The results of this trial are very encouraging and initial conversations with the U.S. Food and Drug Administration have indicated the potential for a streamlined development program given the current unmet need for bipolar and schizophrenia patients who experience episodes of acute agitation,” said Jon Congleton, President and Chief Executive Officer of Impel NeuroPharma. “We are excited that Impel NeuroPharma’s drug-device clinical programs, including INP105, are progressing rapidly and we anticipate multiple data readouts and regulatory filings across the portfolio in the next 18-24 months.”

In the trial, a randomized, double-blind, placebo-and-active controlled, two-period crossover design, the overall safety and tolerability profiles of INP105 were similar to Zyprexa and Zyprexa Zydis. The most common adverse events (at least two events for any treatment) were dizziness (including postural), headache, nasal congestion, rhinorrhea, hypotension, orthostatic hypotension, fatigue, restlessness, nausea and orthostatic tachycardia.

“Unfortunately, the mental health community still lacks an ideal pharmacological rescue treatment for acute agitation – one with a non-invasive route of administration but with rapid onset, adequate duration and good tolerability,” said Michael H. Allen, M.D., Professor of Psychiatry and Emergency Medicine at the University of Colorado. “These data are encouraging as they indicate that INP105 may be able to help patients maintain consciousness and return to a tranquil state so healthcare professionals can better assess and treat them in both hospital and outpatient settings.”

Acute agitation often manifests in people living with serious mental health conditions, such as bipolar I disorder or schizophrenia. Agitation episodes related to neuropsychiatric disorders account for approximately 1.7 million visits to the ER each year, placing a significant economic and resource burden on the healthcare system.1 An ideal medication for acute agitation, according to a 2005 expert consensus, is easy-to-administer, non-traumatically administered, provides rapid tranquilization without excessive sedation, has a swift onset of action with sufficient duration to prevent untimely recurrence, and has low risk for adverse events and drug interactions.2 Such an optimal medication could be suitable for administration earlier during an agitation episode, possibly avoiding the need for ER attendance, as well as reduce the need for injected drugs and the associated risks of needlestick injuries and assaults on healthcare staff.

About the Trial
The “SNAP 101” Trial (Safety and Tolerability of Intranasal POD-olanzapine) is evaluating the safety, tolerability and pharmacokinetic/pharmacodynamic (PK/PD) profile of INP105 at three ascending doses compared with two doses of Zyprexa® intramuscular (5 mg and 10 mg) and orally disintegrating Zyprexa Zydis® (10 mg) in 36 healthy volunteers. The aim of the SNAP 101 trial is to establish the safety and tolerability of INP105 while informing appropriate dosing for future studies based on the PK and PD profiles.

Further details of the SNAP 101 (INP105-101) study can be found on ClinicalTrials.gov.

About INP105
INP105 is a drug-device combination product being studied for the treatment of acute agitation associated with bipolar I disorder or schizophrenia. It is comprised of an intranasal formulation of olanzapine and Impel’s proprietary Precision Olfactory Delivery, or POD, nasal delivery device. The POD device delivers olanzapine to the richly-vascularized upper nasal cavity offering rapid, consistent and optimized bioavailability that can be administered by the patient or a caregiver. Olanzapine is the most commonly used treatment for acute agitation, but its use is limited to intramuscular injection. INP105 is intended to be suitable for use in the hospital emergency room setting as well as early in an episode where it could be self-administered in the patient’s home or supportive care setting.

About Acute Agitation
Acute agitation is defined as excessive motor activity associated with a feeling of inner tension, often manifesting from a number of serious underlying mental health conditions such as bipolar I disorder or schizophrenia. Agitation episodes related to neuropsychiatric disorders account for 1.7 million visits to the emergency room (ER) in the US each year.1 This places a significant burden on ERs, the healthcare system, and the friends and families of those afflicted, and is responsible for many healthcare staff assaults and injuries. The historic approach of “restrain and sedate” is being abandoned in favor of less coercive, more compassionate, de-escalation approaches that include less invasive pharmacologic interventions.

An ideal medication for acute agitation, according to a 2005 expert consensus, is easy-to-administer, non-traumatically administered, provides rapid tranquilization without excessive sedation, has a swift onset of action with sufficient duration to prevent untimely recurrence, and has low risk for adverse events and drug interactions.2

About Impel NeuroPharma
Impel NeuroPharma, Inc., is a privately-held, Seattle-based biotechnology company devoted to creating life-changing, innovative therapies for central nervous system (CNS) diseases. Impel NeuroPharma is currently investigating INP104 (POD-DHE) for acute migraine headache, INP103 (POD-levodopa) for reversal of OFF episodes in Parkinson’s disease and INP105 (POD-olanzapine)  for acute agitation in schizophrenia and bipolar disorders.

Impel’s products utilize its novel, nasal drug-delivery Precision Olfactory Delivery, or POD, device technology to deliver liquid or dry powder forms of drug to the upper nasal cavity in a consistent and predictable manner.

IMPEL, POD and the IMPEL Logo are trademarks of Impel NeuroPharma, Inc. To learn more about Impel NeuroPharma, please visit our website at https://impelnp.com.

Contact:
Melyssa Weible
Elixir Health Public Relations
Ph: (1) 201-723-5805
E: mweible@elixirhealthpr.com

1 Allen MH, Currier GW, Hughes DH et al. J Psychiatr Pract 2005. 11(Suppl 1); 5-108

2 The Diagnosis and Management of Agitation. Edited by Scott L. Zeller, Kimberly D. Nordstrom and Michael P. Watson. Cambridge University Press 2017, Page 1.

Impel NeuroPharma Announces First Patient Dosed in Phase 1 Clinical Trial of INP104 for Treatment of Acute Migraine Headache

Study to Explore Bioavailability and Safety of Novel, Intranasal Dihydroergotamine Delivered via Precision Olfactory Delivery™ Technology

SEATTLE, October 31, 2017 — Impel NeuroPharma, a Seattle-based, privately-held biotechnology company focused on therapies for the treatment of central nervous system (CNS) disorders, today announced that the first patient was dosed in the recently-initiated Phase 1 clinical trial of INP104 for acute migraine headache. INP104 is a novel dihydroergotamine (DHE) product delivered via Impel’s proprietary Precision Olfactory Delivery, or POD™, intranasal delivery platform.

This trial will investigate the comparative bioavailability of INP104 versus two approved DHE formulations – D.H.E. 45 (dihydroergotamine mesylate) intravenous (IV) injection (100% bioavailability), and Migranal® (dihydroergotamine mesylate, USP) Nasal Spray (reported ~32% bioavailability).

DHE is a drug often used in specialist headache clinics for acute migraines, but current methods of administration by injection or traditional nasal spray devices create barriers to their widespread use.

“We believe the consistent, reliable, dose-to-dose delivery of product via Impel’s POD intranasal device holds the promise to improve systemic levels of DHE that were previously unachievable without injection,” said Jon Congleton, chief executive officer of Impel NeuroPharma. “Migraine affects more than 36 million people in the United States, and over a third of these have breakthrough acute migraines that are poorly addressed with currently-available treatments.”

“This Phase 1 bioequivalence trial will provide initial safety and tolerability data for INP104, and if predetermined, comparative bioavailability is proven, these data will serve as the basis for enabling a pivotal safety study of INP104 in 2018, with the intent to file a new drug application (NDA) in 2019,” commented John Hoekman, chief scientific officer and founder of Impel NeuroPharma.

About INP104

INP104 combines a currently approved formulation of dihydroergotamine (DHE) for intranasal delivery with Impel’s novel Precision Olfactory Delivery™ or POD™ technology. The POD device is designed to propel a narrow plume of aerosolized DHE to the upper nasal space. The device is a simple to use patient friendly system that does not require coordination of inhalation with actuation of the device.

This Phase 1 study, INP104-101, is Impel’s first clinical study and is being conducted in Australia. The study will examine comparative bioavailability of three DHE arms, as well as explore safety and tolerability. Further details can be found on the ANZCTR website (www.anzctr.org.au)

About Precision Olfactory Delivery™ or POD™ Technology

Impel NeuroPharma’s proprietary POD intranasal drug delivery platform is designed to deliver drugs to the upper nasal cavity to achieve superior biodistribution and bioavailability of both small molecules and biologic drugs. By delivering therapeutics to the upper nasal cavity, the POD nasal delivery platform may improve overall bioavailability of drugs, and has the potential to target the brain via the olfactory and trigeminal nerves and to improve upon current treatment options for central nervous system (CNS) disorders. Impel has developed dry powder and liquid compatible POD technology.

About Impel NeuroPharma

Impel NeuroPharma, Inc., is a privately-held, Seattle-based company devoted to creating life-changing, innovative therapies for central nervous system (CNS) diseases. Impel’s products are based on a novel nasal drug delivery platform, the POD technology, that administers drug to the upper nasal cavity.

Impel NeuroPharma has is currently investigating INP104 (POD DHE) for acute migraine headache and INP103 (POD levodopa) for Parkinson’s Disease, as well as INP102 (POD insulin) for Alzheimer’s disease in an NIH funded trial.

Impel NeuroPharma’s proprietary POD technology enables entirely new categories of drugs, including biologics, to be administered using a cost-effective, disposable, non-invasive intranasal drug delivery device. To learn more about Impel NeuroPharma, please visit our website at https://impelnp.com.

Contact:
Melyssa Weible
Elixir Health Public Relations
Ph: (1) 201-723-5805
E: mweible@elixirhealthpr.com

Impel NeuroPharma Board Announces Appointment of Jon Congleton as CEO

New CEO will lead Impel’s unique CNS pipeline to the clinic and potential commercialization

Seattle, WA—October 03, 2017—Impel NeuroPharma, Inc., a Seattle based biotechnology company, announced the appointment of veteran biotech executive Jon Congleton as the company’s new President and Chief Executive Officer (CEO). Impel is developing first-in-class intranasal drug treatments for central nervous system (CNS) disorders.

“Impel has made impressive, ground-breaking scientific progress with its CNS pipeline and delivery platform,” said H. Stewart Parker, Impel’s Executive Board Chair. “We are confident that Jon Congleton, with his impressive corporate leadership background and CNS product successes, will now lead Impel’s transition from the lab to regulatory approval and commercialization of its assets.” Impel raised $36 M in a Series C round in December of 2016 to advance its research platform.

Congleton has over 30 years’ experience in biopharmaceutical company leadership including pipeline development, commercial strategy, and general management. Most recently he was President and CEO of Nivalis Therapeutics where he successfully executed the company’s IPO and clinical programs.

“Impel’s unique Precision Olfactory Delivery™ or POD™ nasal delivery platform addresses an underutilized route of administration for therapeutics and can represent a significant breakthrough in drug delivery of both small molecules and biologics,” Congleton stated. “I am very excited to join the Impel team to help further develop the value of its deep pipeline to benefit CNS patients who are vastly underserved with current therapies.”

Parker also praised the tenure of interim CEO, John Hoekman, PhD. John Hoekman, a co-founder of Impel, will remain as Impel’s Executive Vice President and Chief Scientific Officer. Hoekman will also continue on Impel’s Board of Directors. “Dr. Hoekman has played a key role in developing Impel’s POD™ platform and current pipeline. His nasal delivery expertise, creativity, and scientific leadership will be invaluable as we move our company forward,” Parker added.

About POD technology

Impel NeuroPharma’s POD™ nasal drug delivery platform is designed to deliver drugs to the upper nasal cavity to achieve superior biodistribution and bioavailability of both small molecules and biologic drugs in patients. By delivering therapeutics to the upper nasal cavity, the POD nasal delivery platform may improve overall bioavailability and has the potential to target the brain via the olfactory and trigeminal nerves.

About Impel NeuroPharma

Impel NeuroPharma, Inc. is a privately held, Seattle-based company devoted to creating life-changing, innovative therapies for central nervous system (CNS) diseases. Impel NeuroPharma has multiple therapies in clinical development to treat diseases such as migraine, Parkinson’s, and Alzheimer’s. Impel’s products are based on a novel nasal drug delivery platform, the POD™ technology, that administers drug to the deep nasal cavity. Impel NeuroPharma’s proprietary POD ™ device technology enables entirely new categories of drugs, including biologics, to be administered using a cost-effective, disposable, non-invasive intranasal drug delivery device. To learn more about Impel NeuroPharma please visit our website: https://impelnp.com/

Contact: Sutapa Ray, PhD    206-568-1466    info@impelnp.com

Our New Headquarters at 201 Elliott

September 13, 2017 — At the beginning of September, Impel NeuroPharma moved its headquarters to 201 Elliot, a new biotech lab and office building.

“The office gives us the capacity to grow, it takes us from startup mode to small company mode.” Dr. John Hoekman, Impel’s CEO is quoted as saying in an article from the Puget Sound Business Journal.

Read more about our new home in their article, ‘Impel NeuroPharma leases hard-to-find lab space.

Impel wins the International General Counsel Silver Award 2017

July 14, 2017 — This year, Impel NeuroPharma’s legal department was awarded the International General Counsel Silver Award 2017 for the best USA legal department: Pharmaceuticals, Health & Biotech. It was awarded at the International Legal Alliance Summit.

 

 

Neurotech Investing and Partnering Conference – 1 JUN

On Thursday, June 1 at 10:00 am, John Hoekman will be presenting at the 12th annual Neurotech Investing and Partnering Conference focused on drugs, devices, and diagnostics for the brain and nervous system. He will be giving a presentation in the session focused on “Parkinson’s and Movement disorders.”

Now in its 12th year, the Neurotech Investing and Partnering Conference is the premier partnering and investing conference for the neurotechnology industry including pharmaceuticals, medical devices, software and diagnostics for the brain and nervous system. It will be held from May 31 – June 1, 2017 at the Park Central Hotel in San Francisco, CA.

For more information, please visit the conference website at www.neurotechconf.com