Portage Biotech BHV-0223

TORONTO, Nov. 19, 2015 /PRNewswire/ - Portage Biotech Inc. ("Portage") (OTC Market: PTGEF, Canadian Securities Exchange: PBT.U), and Biohaven Pharmaceutical Holding Company Limited (Biohaven), announced today that preliminary results from a Phase I study with BHV-0223, a glutamate modulating agent, met its study objectives and supports advancing the asset into late phase clinical development. BHV-0223 is a unique formulation of a glutamate modulating agent that utilizes the Zydis® ODT fast-dissolve technology under an exclusive worldwide agreement with Catalent. Agents that modulate glutamate neurotransmission may have therapeutic potential in multiple glutamatergically driven disease states including amyotrophic lateral sclerosis (ALS), Alzheimer's disease, Rett syndrome, dementia, dystonia, tinnitus, anxiety disorders, and numerous affective disorders like GAD and OCD.

Affective disorders constitute psychiatric disorders related to anxiety and mood. Despite the significant public health burden of these illnesses and decades of active pharmaceutical research, existing treatments almost exclusively target the monoamine neurotransmitter systems. While there are numerous approved first-line medications for these disorders, most have similar mechanisms of action and many do not experience remission with first or second-line pharmacologic treatments. BHV-0223 targets this unmet need and introduces an agent with a novel mechanism to treat these disorders.

The Phase I trial was designed to demonstrate the safety and unique pharmacokinetic characteristics of BHV-0223 in single and then multiple dosing in humans. In the first phase of the study, approximately 10 participants were treated with varying doses of BHV-0223 on four separate occasions. In the second phase of the trial, participants received multiple daily doses of BHV-0223. The study tested three doses of BHV-0223 along with an oral tablet formulation of the active pharmaceutical ingredient.

Dosing with BHV-0223 showed favorable pharmacokinetic properties and greater exposure than the oral tablet formulation on a dose normalized basis. The pharmacokinetic modeling and analysis of metabolites is pending. The vast majority of adverse events were classified as mild. There were no serious or severe adverse events.

Robert Berman, M.D., Chief Medical Officer of Biohaven commented, "This preliminary data is exciting as it demonstrates that we have designed a truly unique formulation of this glutamate modulating agent with advantages over generic competition. Based upon the preliminary pharmacokinetic, safety and tolerability findings, we are moving forward with our plans to begin clinical trials in early 2016."

The Board of Directors of Biohaven also has appointed Vlad Coric, M.D. as Chief Executive Officer. Dr. Coric has had a distinguished academic and pharmaceutical career with more than 15 years of drug discovery and clinical development experience at Yale University School of Medicine and Bristol-Myers Squibb. Within the pharmaceutical industry, Dr. Coric has worked across therapeutic areas including neuroscience, oncology, immuno-oncology and virology. He has been involved in multiple research and development programs including marketed drugs such as ABILIFY® (aripiprazole; partial dopamine agonist), OPDIVO® (nivolumab; anti-PD1), YERVOY® (Ipilimumab; anti-CTLA-4), DAKLINZA® (daclatasvir; NS5A inhibitor) and SUNVEPRA® (asunaprevir; NS3 inhibitor).

"I am excited to join Biohaven and bring my drug development background from Yale and Bristol-Myers along with my extensive experience working with Dr. Berman on the glutamatergic system to Biohaven," said Dr Coric. He added, "I believe our team is well-positioned so that we are not just a neuroscience opportunity but a company that can address multiple pathologies associated with the glutamate."

About Biohaven

Biohaven is a privately-held biopharmaceutical company engaged in the identification and development of clinical stage compounds targeting the glutamatergic system. The company has licensed intellectual property from Yale University and Massachusetts General Hospital. Biohaven is owned by a group of investors including Portage Biotech Inc. (OTC Market: PTGEF, Canadian Securities Exchange: PBT.U), Yale University and other private investors. The company's first drug candidate, BHV-0223, is a novel formulation of a glutamate-modulating agent, being developed under FDA 505(b)(2) guidelines. BHV-4157, a prodrug form of the same glutamate modulating agent, is being developed as a New Chemical Entity (NCE). The FDA cleared the company's Investigational New Drug application (IND) in August 2015 and BIOHAVEN has completed a PK study in humans with the final study report expected by 4Q2015 to enable the Phase 2/3 start in 2016. The company plans to advance other glutamatergic approaches and is actively exploring licenses for additional compounds.

About Portage:

Portage is engaged in identifying, financing and developing novel therapeutics in indications with high unmet medical need. Portage plans to add 5-7 other opportunities to its portfolio either by direct investment into a company, spinout from academia, or through the creation of an SPV with another company or management team

Apart from Biohaven, Portage also has fully owned subsidiary, Portage Pharmaceuticals Limited (PPL). PPL has successfully validated a new proprietary cell permeable peptide platform technology that has been shown to efficiently deliver an active pharmacological agent or cargo into a cell without disrupting the cell membrane. PPL will be advancing its lead candidate, PPL-003, to an Investigational New Drug (IND) application for the topical treatment of dry eye disease and uveitis. PPL recently completed a study in a rat model of dry eye disease in which a topical PPL-003 solution achieved highly significant efficacy and a more rapid onset of action than topical 0.1% dexamethasone.

Portage has also invested in Sentien Biotechnologies Inc., a Boston based private company developing an extracorporeal bioreactor for the delivery of cell therapies. This summer, Sentien completed a financing that will allow it to finish IND enabling studies and a Phase I trial.

For further information, contact Dr. Greg Bailey, the Chairman at gb@portagebiotech.com or Kam Shah, Chief Financial Officer, at (416) 929-1806 or ks@portagebiotech.com or visit our website at www.portagebiotech.com.

Forward-Looking Statements

This news release includes forward-looking statements within the meaning of the U.S. federal and Canadian securities laws. Any such statements reflect Portage's current views and assumptions about future events and financial performance. Portage cannot assure that future events or performance will occur. Important risks and factors that could cause actual results or events to differ materially from those indicated in our forward-looking statements.

Portage assumes no obligation and expressly disclaims any duty to update the information in this News Release.



SOURCE Portage Biotech Inc.

 

BHV-0223 is a glutamate modulating agent formulated using the Zydis® ODT fast-dissolve technology under an exclusive worldwide agreement with Catalent. The Zydis® orally disintegrating tablet (ODT) fast-dissolve is a unique, freeze-dried oral solid dosage form that disperses instantly in the mouth - no water is required. With more than 20 products launched in 50 countries, Zydis® is the World's best-in-class, ODT technology. Catalent is the industry leader for drug development technology. BHV-0223 is also protected by methods of use intellectual property licensed from Yale University School of Medicine.

BHV-0223 is being developed for eventual commercialization in treatment-resistant anxiety disorders, focusing initially on Generalized Anxiety Disorder (GAD). The mechanism of action of BHV-0223 involves the modulation of glutamate. Recent scientific findings have linked a variety of central nervous system and other diseases with altered glutamate function. These findings suggest that agents that modulate glutamate neurotransmission may have therapeutic potential for treating multiple treatment-resistant disorders. Potential target indications thought to involve glutamate neurotransmission include amyotrophic lateral sclerosis (ALS), Alzheimer's disease, Rett syndrome, dementia, dystonia, tinnitus, anxiety disorders, affective disorders and a variety of cancers.

 

Well, that's interesting. Altered glutamate function is also associated with a variety of cancers. I am now curious to know how many tinnitus sufferers also have one or more of the other disorders. Certainly anxiety disorder seems to be a common partner, but I don't know if it's the chicken or the egg.

From their website, the bio of their Chief Scientific Officer:

Dr. Marcoux has over 25 years of pharmaceutical company and academic research experience. He was the VP of Quantitative and Innovative Medicine in WW Development at Pfizer and former VP WW Discovery Biology Discipline Head until 2008 when he became an independent consultant. Previously he worked for Parke-Davis Pharmaceutical Research, for seventeen years. Dr. Marcoux’s consulting focus is on high confidence translation of drug discovery programs to early clinical proof of concept and is aimed at biotech, pharma and academic medical centres. Dr. Marcoux holds a Ph.D. in Physiology and Biophysics and has held research positions prior to industry at Harvard Medical School/Massachusetts General Hospital, University of Alabama, Birmingham, Medical Center, and at the University of Vermont, College of Medicine.

His LinkedIn page:
https://www.linkedin.com/in/frank-w-marcoux-b1492b3

Thanks @Danny Boy

 

Too bad that all these trials and research weren't done 10 years ago

Anyway, it's good that there is one more possible treatment coming and they seem to be advancing to clinical trials with haste (vs. AM-101 which has been under development for...10 years?).

Most of my relatives from both sides of my parents (like 80%) have died because of cancer so I'm pretty sure I'm included in the risk group.

 

NMDA receptor modulators (glutamate modulators) are a new form of antipsychotic that are in Phase II FDA study. The first compound studied was glycine which was hypothesized by Daniel Javitt after observation that people with phencyclidine(PCP)-induced psychosis were lacking in glutamate transmission.[1] (PCP is an NMDA receptor antagonist that blocks glutamate) In giving glycine to people with PCP-induced psychosis a recovery rate was noted. From there, it was hypothesized that people with psychosis from schizophrenia would benefit from increased glutamate transmission and glycine was added with strong recovery rates noted especially in the area of negative and cognitive symptoms. Glycine, however, sporadic results aside (dose 60 g/day or 0.8 g/kg,[2][3] approximately the amount in 300 g of gelatin powder or two kilograms of sunflower seeds[4]) remains an adjunct antipsychotic and an unworkable compound. However, the Eli Lilly and Company study drug LY2140023 is being studied as a primary antipsychotic and is showing strong recovery rates, especially in the area of negative and cognitive symptoms of schizophrenia.Tardive dyskinesia, diabetes and other standard complications have not been noted:

Treatment with LY2140023, like treatment with olanzapine, was safe and well-tolerated; treated patients showed statistically significant improvements in both positive and negative symptoms of schizophrenia compared to placebo (P o 0.001 at week 4). Notably, patients treated with LY2140023 did not differ from placebo-treated patients with respect to prolactin elevation, extrapyramidal symptoms or weight gain. These data suggest that mGlu2/3 receptor agonists have antipsychotic properties and may provide a new alternative for the treatment of schizophrenia.[5]

Other NMDA receptor modulators are being studied and this modality of treatment may once approved as antipsychotic medications gradually replace the current (dopaminergic) antipsychotics.

 

https://alsnewstoday.com/2016/03/04...-and-expedited-development-path-for-bhv-0223/


"Portage Biotech and Biohaven Pharmaceuticals recently announced they have received positive feedback from the U.S. Food and Drug Administration (FDA) on their Pre-Investigational New Drug Application (PIND) interaction regarding Biohaven’s investigative drug BHV-0223, intended for treatment of amyotrophic lateral sclerosis (ALS).

BHV-0223 is the glutamate modulating compound riluzole, contained in the tablet formulations Zydis ODT fast-dissolve technology. The drug will be produced under an exclusive worldwide agreement with Catalent, which makes Zydis.

Glutamate modulating drugs are of interest for a number of diseases in addition to ALS, such as Alzheimer’s disease, Rett syndrome, dementia, dystonia, tinnitus, anxiety disorders, and affective disorders.

The formal correspondence from the FDA came after an in-person meeting, and detailed clinical, nonclinical, and regulatory issues for the drug. The feedback correspondence also discussed the trial design of the Investigational New Drug (IND) opening clinical trial and a proposed development plan for ALS.

In a press release, Biohaven says the FDA response contained no issues that could delay the planned bioequivalence trial in 2016. The FDA also agreed that Biohaven does not need to provide additional efficacy or toxicology studies before submission of the New Drug Application. The FDA also agreed that for ALS, the 505(b)2 regulatory pathway is acceptable for BHV-0223. The pathway is a faster track than a full application, and is usually reserved for new products with well-studied ingredients.

“We now have a clear regulatory path forward for BHV-0223 in ALS. The responses we received from FDA were aligned with our expectations, and no material issues were raised that would delay the timely initiation of our bioequivalence study,” said Vlad Coric, CEO of Biohaven, in the press release.

“Our clinical program will expand upon our existing data with BHV-0223 and the goal will be to establish bioequivalence to the active pharmaceutical ingredient (riluzole) with lower doses of our new formulation. After we establish bioequivalence in the upcoming trial and demonstrate the advantages of this formulation to patients, we will be in position for a timely NDA submission. We believe that the enhanced formulation, dosage and route of administration of BHV-0223 will benefit patients with this devastating disease,” Coric said.

Declan Doogan, CEO of Portage and chairman of Biohaven, said, “The Biohaven team continues to demonstrate their ability to develop and execute on their strategy for BHV-0223. Biohaven will next take steps to prepare for an anticipated commercialization of the investigational agent upon successful results from the planned bioequivalence study. This will allow Biohaven to progress rapidly into the clinic and then to the market after NDA approval. The obligations are much less than a standard new drug application. We are very pleased with Portage investment in Biohaven, a company with a great team and an exciting product line.”

 

So since this med will work on glutamate, can we say benzo induced tinnitus can be cured(at least reduced) by this drug? I'm sorry I'm not good at scientific things that is why my question may seem stupid.

 

Can we say this drug and memantine work the same way? But this drug looks like more efficient? I know memantine can work for benzo related tinnitus and this is why these studies excite me.

 

Aren't these drugs which are not very specific targeted at Tinnitus, like shooting with a cannon on a mosquito? It's not like we want more havoc done.

 

This drug is currently in Phase 3 Clinical Trials with an estimated completion on August 2017.

https://clinicaltrials.gov/ct2/show/NCT02960893

 

The phase 3 trial is about BHV-4157 (Ataxia) and not about BHV-0223 (ALS). Also don't know why this thread exists since the candidate compound is not purposed for tinnitus (with this logic we need to add every one of the 100 trailed drugs that enacts on the brain...).

So... please read and think properly before posting unusefull / random posts!

 

@Mic

http://biohavenpharma.com/biohaven-...w-drug-application-ind-approval-for-bhv-4157/

And Oops you're right I did post in the wrong drug thread for this company. I'm not going to bother anymore. I'm tired of getting barked at.

 

Might have this...might have that... big pharma behaviour as usual...

Maybe they can also add to the list that this new drug might be improve our chances of winning the Powerball lottery...

And @NatureHiker ... nobody is barking at you... it is just a small request for more focus on evidence based research instead of wishful thinking on every brain drug trial we encounter...

 

Listen up. I only posted here because one of the conditions listed that it has the potential to treat is Tinnitus. And it goes through the same FDA trials as all other drugs. I have no other motive here than just being helpful and sharing news.

If you want to go on a rant on how big Pharma will never cure cancer or diabetes because they are cash cows go ahead. But I'm utterly tired of hearing all that overwhelmingly pessimistic bullshit. It's annoying. Isn't there somewhere else you can do that???

And I'm sorry to take up your precious forum space. Where other topics like human head transplants, colored light therapy, and trying ecstasy to treat Tinnitus are being discussed. I agree those are way more relevant than this drug. This drug is absolutely nothing and will never have any implications for Tinnitus in the future. Again sorry for wasting your forum space and making your finger having to scroll just a tad bit further.

 

Wow... @NatureHiker ... you do have some good qualities for dramatizing things up, don't you? Pittyfishing in a pool of likeminded won't help in this.

What helps is avoiding sophistry and doing solid research before posting things. Thinking before you come up with something is not about pesimisim or optimism... It's about realism!

Having said this I hope you still stay on this forum. Turning your back to discussions will not help anybody.

 

Listen i don't want to get mixed up in all your drama. I'm going to continue posting stuff that is indeed relevant to tinnitus and if you don't like it then just ignore it and go to a different thread.

I hope that resolves the issue.

And so i get on track... BHV-4157 is a glutamate modulating drug. Glutamate modulation in regards to tinnitus has been widely discussed and researched. Namenda (mematine), Gabapentin, cannabinoids, Acamprosate are various drugs that have been discussed here on tinnitustalk which are theorized to help tinnitus by modulating glutamate.

Here is a list of all the tinnitustalk threads discussing 'glutamate' here on tinnitustalk:

https://www.google.com/search?q=glu...F-8#q=glutamate+site:tinnitustalk.com&start=0

 

Thank you very much that you made me laugh for the past 5 minutes @NatureHiker . Your capability to invert things up is wonderfull.

Now... if you don't mind a little critical remark... would you please place your posts about BHV-4157 in the threads that are available for this compound. To help you a little bit below a screenshot of 2 corresponding threads:


Thanks in advance,
Mic

P.S.: Surprised that you didn't find these threads by yourself with your tremendous googling capabilities

 

I acknowledged that I posted in the wrong drug thread for biohaven in my first response to you. My other replies have simply been to just remind you that this research is relevant to tinnitus. Cheers!