Intellect Neurosciences Inc. (OTCBB: ILNS) is a biopharmaceutical company engaged in the discovery and development of a new breed of innovative "disease-modifying" therapeutic drugs that are designed to slow, arrest and ultimately prevent Alzheimer's disease and other serious neurodegenerative disorders.
Intellect is focused on neurodegenerative conditions collectively known as proteinopathies such as Alzheimer's, Parkinson's and Huntington disease. Proteinopathies are caused by amyloidogenic proteins, such as amyloid beta, tau, alpha synuclein and Huntingtin. Intellect is the first company to develop antibody drug conjugates (ADCs) in which amyloid clearing antibodies are empowered by chemically linking them to molecules that offer neuroprotection, creating a single drug. The use of ADCs is one way in which Intellect is developing more effective drugs with the recognition that monotherapy may not be effective enough in treating the complex nature of proteinopathies.
A second approach being pioneered by Intellect, also based on this idea and specifically focused on Alzheimer's disease, is a bi-specific vaccine that targets both beta amyloid and a pathogenic form of tau protein. In contrast to antibodies that only target beta amyloid and have not yet proven their ability to treat mild to moderate Alzheimer's disease, the dual target vaccine being developed by Intellect has the potential to be used both prophylactically in presymptomatic patients and therapeutically in patients that are symptomatic.
Intellect Neurosciences has its origins in some of the earliest pioneering work that stimulated the development of the potential disease-modifying monoclonal antibodies that several global pharmaceutical companies have been testing as treatments for Alzheimer's disease. The intellectual property resulting from the discovery of how such antibodies could be used as treatments predates competitive strategies such that the pharmaceutical companies developing those drugs, purchased licenses to the technology from Intellect. The company remains ahead of the curve with respect to next-generation therapies, as it has developed multiple distinctive platform technologies that are generating drug candidates for a wide variety of diseases.
The company developed OX1, a multimodal antioxidant molecule, through preclinical and human safety trials before licensing the program to ViroPharma. ViroPharma has said it plans to enter Phase 2 clinical trials in patients with Friedreich's Ataxia, an orphan indication, in 2013. Intellect could receive in excess of $100 million in milestone payments from ViroPharma and, if approved, royalties from sales over many years.
Intellect's preclinical R&D pipeline is based on two proprietary platform technologies, CONJUMAB-A and RECALL-VAX and includes the following drug candidates:
CONJUMAB-A: Empowered Antibodies for the Treatment of Proteinopathies
N01-OX2 is a first-in-class ADC. It is a humanized monoclonal antibody specific for beta amyloid protein that is empowered to deliver on-site neuroprotection by its conjugation to melatonin. The goal of N01-OX2 is to reduce the oxidative stress that leads to cellular inflammation and damage. N01-OX2 is being developed for the treatment of age-related macular degeneration (AMD), the leading cause of blindness in people over the age of 55. AMD therapies generate $4 billion annually, even though the few approved treatments don't cure the disease and offer only modest improvements in vision for most patients. N01-OX2 also has potential applications for diabetic retinopathy, glaucoma, traumatic brain injury and Alzheimer's disease.
T01-OX2 is an ADC comprised of a monoclonal antibody selective for oligomeric toxic forms of tau protein and is empowered with neuroprotection by its conjugation to melatonin. T01-OX2 is expected to reduce tau pathology and has potential for the treatment of Alzheimer's disease, Frontotemporal dementia and also has potential applications to treat ophthalmology indications.
RECALL VAX: A chimeric peptide vaccine comprised of a human B cell epitope linked to a bacterial T cell epitope to produce highly specific vaccines against one or more amyloidogenic proteins.
RV03 is a first-in-class bi-specific vaccine targeting both beta amyloid and delta tau. Delta tau is a shorter form of the tau protein. It is especially toxic to nerve cells and precedes the formation of neurofibrillary tangles. RV03 has potential for the treatment of Alzheimer's disease and Frontotemporal dementia. http://www.intellectns.com/
(Resigned for cause) see accompanying notes below.
Founder Intellect Neurosciences
Daniel G. Chain, Ph.D., Chief Executive Officer. Dr. Chain formed Intellect in April 2005 and has served as our Chief Executive Officer since October 2005. In July 1999, Dr. Chain founded Mindset Biopharmaceuticals USA, Inc., a biopharmaceutical development stage company, and Mindset Ltd., an Israeli research and development subsidiary of Mindset Biopharmaceuticals USA. In 2001, Dr. Chain founded MindGenix Inc., a contract drug testing company, as a subsidiary of Mindset Biopharmaceuticals USA. He served as Chief Executive Officer of Mindset Biopharmaceuticals USA from July 1999 until October 2005, when he resigned as the Chief Executive Officer of Mindset Biopharmaceuticals USA and joined Intellect. Dr. Chain continues to serve Mindset BioPharmaceuticals USA and MindGenix as president of both companies. Under his employment agreement with us, he is permitted to spend up to 5% of his time in his capacity of president of Mindset Biopharmaceuticals and Mindgenix. Dr. Chain is the author of several scientific research publications in peer-reviewed journals in various fields. Dr. Chain's interest in biology of the human brain led to his invention of antibody-based therapies being developed for the prevention and treatment of Alzheimer's disease and to the invention of insulin sensitizers being developed to increase glucose utilization in the aging brain as a method to improve age-related cognitive impairment. Dr. Chain is a member of the Society for Free Radical Biology and Medicine, a member of the Royal Society of Medicine and the Society for Neuroscience. Dr. Chain obtained his B.Sc., with honors, in Biochemistry from the Institute of Biology in London and obtained his Ph.D. in Biochemistry from the Weizmann Institute of Science in Israel. He trained as a post-doctoral research fellow at the Center for Neurobiology and Behavior at Columbia University College of Physicians and Surgeons in New York. Dr. Chain is qualified to be a director of the Company based on his prior experience as a CEO and a director of biotechnology companies.
Intellect's preclinical R&D pipeline is based on four proprietary platform technologies: ANTISENILINÒ, CONJUMAB™, OLIGOTOPE™ and RECALL-VAX™
ANTISENILIN®: Free-end Specific Amyloid Beta Antibodies for Treatment of AD
IN-N01 is a humanized a high-affinity, stabilized, IgG4 therapeutic antibody that binds the amino terminus of amyloid beta without binding to the amyloid precursor protein (APP).
Antibodies exist in several isoforms; IgG1 antibodies have the strongest potential to induce inflammation while IgG4 has the lowest potential. IN-N01 is designed to promote the clearance of monomeric, oligomeric and plaque forms of amyloid beta, which accumulate in the brains of Alzheimer's patients or following traumatic brain injury and in the retina of the eye in patients with age-related macular degeneration, diabetic neuropathy and glaucoma.
CONJUMAB™: Empowered Antibodies for the Treatment of Proteinopathies
CONJUMAB-A is a first-in-class antibody drug conjugate for treatment of proteinopathies. IN-N01 has been empowered to deliver on-site neuroprotection by its conjugation to melatonin. Melatonin is a potent free radical scavenger and is an inhibitor of beta amyloid aggregation and previously shown to counteract the neurotoxicity associated with amyloid beta. Compounds based upon CONJUMAB-A are designed to reduce the oxidative stress and promote clearance of beta amyloid that is central to cellular inflammation and damage.
CONJUMAB-A is being developed for the treatment of age-related macular degeneration (AMD), the leading cause of blindness in people over the age of 55. CONJUMAB-A also has potential applications for diabetic retinopathy, glaucoma, traumatic brain injury, and Alzheimer's disease.
OLIGOTOPE™: Protein oligomer selective antibodies and methods of making them using chemically cross-linked stabilized aggregates as immunogens
TOC-1, our first compound utilizing the OLIOGOTOPE platform, is a murine monoclonal antibody selective for neurotoxic tau oligomers or aggregates considered to be the earliest pathogenic form of tau. Intellect plans to test TOC-01 as potential therapeutic for Alzheimer's disease and other tauopathies such as Frontotemporal dementia.
TauC3 specifically targets the neoepitope that is formed following cleavage of intact tau protein by proteolytic enzymes known as "executioner" caspases. This pathological process is stimulated by an accumulation of amyloid beta in the brain of Alzheimer's patients. It is believed that the smaller cleaved tau, referred to as delta tau, is especially toxic and prone to form tangles inside nerve cells and occurs early in the pathogenesis of the disease so antibody-mediated removal of delta tau would be expected to prevent the irreversible damage to nerve cells.
RECALL VAX™: Chimeric peptide vaccine platform incorporating bacterial and human epitopes to target neoepitopes in pathological proteins
RV03, our first compound generated on the RECALL-VAX platform, is a first-in-class bi-specific vaccine targeting both beta amyloid and delta tau. Delta tau is a shorter form of the tau protein. It is especially toxic to nerve cells and precedes the formation of neurofibrillary tangles. RV03 has potential for the treatment of Alzheimer's disease and Frontotemporal dementias.
INTERNAL PIPELINE Intellect Neurosciences has two preclinical programs it is developing internally.
One program under the RECALL-VAX platform has yielded two AD vaccine drug candidates, RV01 and RV02. RECALL-VAX™ has the potential to delay or prevent the development of Alzheimer's in those who are at risk by stimulating patients' immune systems to produce antibodies that clear amyloid betas and prevent further accumulation and deposition. Many view a vaccine of this nature, which is analogous to a flu shot, as the ultimate quest in Alzheimer's research.
Additionally, CONJUMAB-A is Intellect's newly introduced platform technology for a novel class of therapeutics for treatment of Alzheimer's disease and other proteinopathies based on antibody-drug conjugates (ADCs). The new ADC- based technology has the potential to improve on current methods of passive immunotherapy by increasing clearance of amyloid proteins while delivering potent cytoprotective molecules to sites of damage in the brain and other organs. CONJUMAB-A is designed to reduce inflammation caused by amyloidosis while avoiding vasogenic edema, a side effect of plaque dissolution that occurs in some patients. The company's lead CONJUMAB-A candidate is IN-N01-OX2, a non-activating, stabilized IgG4 humanized antibody specific for beta amyloid protein conjugated to melatonin, which is a naturally occurring molecule with potent anti-oxidant and anti-fibrillogenic properties.
The Company has applied for a patent for its CONJUMAB-A technology. Intellect has the exclusively license to certain patents granted by the USPTO to NYU School of Medicine and the University of South Alabama Research Foundation specifically covering the use of melatonin for the treatment of Alzheimer's disease and other types of amyloidosis. The CONJUMAB-A platform is applicable to a broad range of diseases including, Alzheimer's, Parkinson's, Huntington's, Age-Related Macular Degeneration, Glaucoma, Cerebral Angiopathy, Frontotemporal Dementia, Progressive Supranuclear Palsy, Pick's disease, Cortical Basal Degeneration and Peripheral Amyloidosis.
OneMedForum San Francisco 2012
January 11-14, 2012
FINDING THE ANSWER TO ALZHEIMER'S
LATEST NEWS / LETTER TO SHAREHOLDERS
Former ‘King of Biotech’ settles with SEC
By Bernard Vaughan
NEW YORK | Thu Aug 22, 2013 8:18pm EDT
(Reuters) - An investor formerly known as the "King of Biotech" has reached a settlement with the U.S. Securities and Exchange Commission over a market manipulation scheme, according to court documents filed on Thursday.
David Blech, who earned the nickname as a founder of companies and a major investor in the biotechnology sector, agreed to pay $1.03 million in disgorgement and interest for the scheme.
In 2012 the SEC had accused Blech of buying and selling significant amounts of stock in two biopharmaceutical companies, Pluristem Therapeutics Inc and Intellect Neurosciences Inc through more than 50 brokerage accounts he established in the names of family and friends in order to create an artificial appearance of activity in the stocks.
The SEC complaint further accused Blech, who had already been convicted of securities fraud in 1998, of selling investments for biopharmaceutical companies despite being barred from acting as a broker-dealer. It also accused him and his wife, Margaret Chassman, of violating federal securities laws by making unregistered sales of securities and failing to disclose their transactions in brokerage accounts.
Chassman agreed to pay close to $550,000 in disgorgement, interest and a civil penalty, according to the settlement.
The settlement was approved by Magistrate Judge Sarah Netburn in Manhattan federal court.
"He's pleased to be putting this episode behind him," Roland Riopelle, a lawyer for Blech, said on Thursday.
A lawyer for Chassman declined to comment.
In May, Blech was sentenced to four years in prison after pleading guilty in a related criminal case to stock manipulation stemming from his trades in Pluristem and Intellect.
The case is USA v David Blech, U.S. District Court, Southern District of New York, No. 12-cr-00372.
(Reporting by Bernard Vaughan; Editing by Chris Gallagher)
Form 8-K for INTELLECT NEUROSCIENCES, INC.
Other Events, Financial Statements and Exhibits
Item 8.01. Other Events.
On July 30, 2013, Intellect Neurosciences, Inc. (OTCBB: ILNS) issued a press release announcing that it has retained Dr. Daniel Chain, though Chain Pharmaceuticals LLC, as a consultant to assist the company in managing its patent estate and external collaborations and pursuing strategic alternatives for the company, which may include partnerships, strategic business model alternatives, a sale or other transaction. Dr. Chain, Intellect's founder, former Chairman and CEO, inventor of the company's technology platforms and developer of its ongoing programs, is uniquely qualified to assist the company in its efforts to maximize the value of Intellect's unique collection of high value assets.
In connection with the engagement of Chain Pharmaceuticals, LLC, the company and Dr. Chain entered into mutual releases of all claims against each other, in particular, a release by the company of Dr. Chain from any claim related to Dr. Chain's involvement with the development of CHF5074, a drug product candidate designed as a treatment for early stage Alzheimer's disease. CHF5074 is currently owned by Chiesi Farmaceutici S.p.A., a pharmaceutical company based in Parma, Italy.
A copy of the press release is attached hereto as Exhibit 99.1 and is incorporated herein in its entirety by reference.
Item 9.01 Financial Statements and Exhibits. http://biz.yahoo.com/e/130812/ilns8-k.html
The following exhibit is furnished as part of this Report on Form 8-K:
99.1 Press Release dated July 30, 2013
Intellect Neurosciences Retains Chain Pharmaceuticals LLC
NEW YORK, July 30, 2013 (GLOBE NEWSWIRE) -- Intellect Neurosciences, Inc. (ILNS) announced today it has retained Chain Pharmaceuticals LLC as a consultant to assist the company in managing its patent estate and external collaborations and pursuing strategic alternatives for the company, which may include partnerships, strategic business model alternatives, a sale or other transaction.
"We are delighted Dr. Daniel Chain has agreed to return to Intellect as a consultant and assist us with our strategic options," said Elliot M. Maza, Consulting Chief Financial Officer and Director of Intellect Neurosciences. "As the founder of Intellect, Dr. Chain is uniquely qualified to assist us in our efforts to maximize the value of Intellect's unique collection of high value assets." http://finance.yahoo.com/news/intellect-neurosciences-retains-chain-pharmaceuticals-153000033.html
Intellect Neurosciences Engages Evli Corporate Finance to Explore Strategic Alternatives to Maximize Shareholder Value Press Release: Intellect Neurosciences, Inc. – Tue, Jun 18, 2013 11:31 AM EDT
NEW YORK, June 18, 2013 (GLOBE NEWSWIRE) -- Intellect Neurosciences, Inc. (ILNS), a biopharmaceutical companyengaged in the discovery and development of treatments for the prevention and treatment of neurodegenerative diseases, announced today that its Board of Directors has engaged Evli Corporate Finance to assist the company with the exploration of strategic alternatives. The Board of Directors is undergoing astrategic review of the feasibility and relative merits of various financial strategies for the company, which may include partnerships, strategic business model alternatives, a sale or other transaction.
Evli Corporate Finance is part of Evli Bank Plc, which is an independent investment and wealth management bank whose clients are institutions, companies and high net worth individuals. TheEvli Group, with headquarters in Finland, has through its corporate finance operations significant experience in working with development companies in the pharma and medtech industries.
Elliot Maza, a director of the company, commented, "We have selected Evli Corporate Finance for this strategic review because of Evli's extensive international relationships in the pharmaceutical industry. Several of our potential partners are based in Europe where Evli has deep and widespread relationships. Evli shares the Board of Directors' belief that the company's asset portfolio, which includes our license of OX1 to ViroPharma, Inc. for the development of a treatment for the orphan disease, Friedreich's Ataxia, TauC3, our ongoing program to develop an alternative compound for the treatment of Alzheimer's disease, and CONJUMAB-A, our novel approach for the treatment of age related macular degeneration, represents a unique mix of high value assets."
In making this announcement, Intellect offers no assurance that the review of possible alternativeswill result in a sale or related transaction and the company does not intend to disclose developments until such time as the Board of Directors approves or has a transaction(s) to recommend to stockholders, or otherwise deems further disclosure appropriate.
Intellect Neurosciences, Inc. Issues Letter to Shareholders
Press Release: Intellect Neurosciences, Inc. – Thu, Jun 20, 2013 9:25 AM EDT
NEW YORK, June 20, 2013 (GLOBE NEWSWIRE) -- Intellect Neurosciences, Inc. (ILNS), a biopharmaceutical companyengaged in the discovery and development of treatments for the prevention and treatment of neurodegenerative diseases, issued the following Letter to Shareholders from Elliot Maza, a member of the Board of Directors of the company.
I would like to update you regarding the company's ongoing programs and business strategy following the recent resignation of our Chairman and CEO, Dr. Daniel Chain.
Status of ongoing programs
OX1 license to ViroPharma, Inc.
Our September 2011 license agreement with ViroPharma, Inc. remains in full force and effect. The agreement grants ViroPharma an exclusive royalty-bearing right and license under Intellect's OX1 technology. Intellect licensed OX1 from NYU and the University South Alabama Medical Science Foundation under a license agreement that remains in effect.
ViroPharma is developing VP20629 (OX1) for the development of a treatment for the orphan disease, Friedreich's Ataxia. The company has reported that the FDA accepted its IND for VP20629. ViroPharma expects to initiate a study in patients by the second half of 2013 and intends to file for Orphan Drug Designation upon review of the Phase 2 proof of concept data. Intellect is entitled to significant milestones payments and royalties upon successful development and commercialization of VP20629.
TauC3 Alzheimer's drug candidate
Intellect's exclusive license from Northwestern University to TauC3 for all therapeutic and diagnostic applications remains in full force and effect. TauC3 is a high affinity IgG monoclonal antibody that uniquely binds to Asp421 at the C-terminus of Δtau, believed to be an important mediator in tau pathology.
Intellect is collaborating with Dr. Frank LaFerla at University of California Irvine to test the therapeutic and prophylactic potential of TauC3 in a triple transgenic mouse model of Alzheimer's disease that exhibits both Aβ and Tau pathologies. Recently, Dr. LaFerla's group at UCI completed the animal testing and currently is accumulating the data and preparing a report describing the results of the experiments. We intend to share those results with you promptly upon receipt. Several pharmaceutical companies have expressed interest in our TauC3 program as it represents a first in class and novel alternative therapeutic treatment for AD.
CONJUMAB-A, protected by patents assigned to Intellect by Dr. Chain, is a humanized monoclonal antibody specific for amyloid beta (Aβ). Its uniqueness is that the antibody is chemically conjugated through a maleimide-based linker to N-acetyl 5-methoxytryptamine (aka melatonin), a potent antioxidant that also has anti-amyloidogenic, anti-inflammatory and anti-apoptotic properties. We are promoting CONJUMAB-A as a particularly effective therapeutic candidate for Age Related Macular Degeneration (AMD), the leading cause of blindness in elderly people. Our enthusiasm is based in part on evidence from studies in preclinical models suggesting that Aβ passive immunotherapy administered systemically can protect against retinal degeneration in glaucoma1 and AMD. CONJUMAB-A offers the possibility to deliver high concentrations of neuroprotective molecule to sites of lesions in the eye.
Engagement of Evli Corporate Finance
Recently we announced that the Board of Directors has engaged Evli Corporate Finance to assist the company with the exploration of strategic alternatives. The Board of Directors is undergoing a strategic review of the feasibility and relative merits of various financial strategies for the company, which may include partnerships, strategic business model alternatives, a sale or other transaction.
Evli Corporate Finance is part of Evli Bank Plc, which is an independent investment and wealth management bank whose clients are institutions, companies and high net worth individuals. TheEvli Group, with headquarters in Finland, through its corporate finance operations, has significant experience in working with development companies in the pharmaceutical and medtech industries. In October 2011, Evli Corporate Finance acted as Advisor to Duocort Pharma upon the sale of the company to ViroPharma.
Search for Chief Scientific Officer
The Board of Directors has initiated a search for a chief scientific officer who will engage with our contract research organizations and potential pharmaceutical company collaborators regarding our ongoing programs. We have identified two outstanding candidates and intend to extend an employment offer shortly.
Our ongoing dispute with Pfizer concerning Pfizer's failure to pay Intellect a milestone payment continues in the judicial process. In May, we served papers in opposition to Pfizer's motion to dismiss our complaint. We remain confident about prevailing in this dispute.
Intellect has a bright future ahead. We are confident in our ability to attract new leadership who will lead the company to success. Thank you for your support.
Elliot Maza, JD, CPA
Member of the Board of Directors and Consulting CFO
Intellect Neurosciences Sues Pfizer Over $2 Million Milestone Payment
Intellect Neurosciences (OTCQB: ILNS), a junior biotech conducting research regarding proprietary drug candidates to treat Alzheimer's disease (AD) and other diseases associated with oxidative stress, said this morning that it has filed a lawsuit in the New York State Supreme Court against a top tier global pharmaceutical company for breach of the licensing agreement between the parties.
The lawsuit has been in the making since the U.S. Patent and Trademark Office issued Intellect a patent in May covering the company's ANTISENILIN® monoclonal antibody platform technology for the treatment and prevention of Alzheimer's disease. The patent is a fundamental component of a licensing agreement between Intellect and an unnamed major pharma. Intellect believes that the allowance of the patent triggered a milestone payment of $2 to Intellect, but the big drug maker does not agree.
As with many licensing agreements, names are not disclosed as part of non-disclosure agreements, so gleaning the name of the global pharma from the news was impossible, but not too difficult to track-down. First, an article published through Accesswire on July 15 offered commentary in saying,
"A news story from Reuters reports that the findings offer a bit of evidence that the drug, bapineuzumab, which is being developed jointly by Pfizer Inc, Irish drugmaker Elan, and Johnson & Johnson is having a desired effect. The news comes on the heels of a report from BioMedReports, a news portal which revealed for the first time on Tuesday that several big pharmaceutical companies originally licensed the drug's technology platform from Intellect Neurosciences (ILNS.OB) after the company's founder and chairman, Dr. Daniel G. Chain discovered and protected the humanized monoclonal antibody." Further, a press release from Intellect issued via PR Newswire on June 24, 2008 stated,
"Intellect recently announced that it has granted a royalty-bearing license to Wyeth and Elan Pharma International Ltd. (Elan) regarding patents and patent applications related to antibodies and methods of treatment for Alzheimer's disease including a co-exclusive license to Bapineuzumab under the ANTISENILIN(R) patents."
Since Pfizer bought Wyeth for $68 billion, "connecting-the-dots" lead to a common thread of the lawsuit being against Pfizer (NYSE: PFE) as the defendant in the lawsuit is unnamed and Elan's (NYSE: ELN) name doesn't seem to be under and NDA.
A search with the New York State Supreme Court systeme confirmed that Pfizer is the defendant in the case that was filed on September 21, 2012.
The due diligence was not really necessary as the web search revealed Pfizer, but it did provoke the thought that Intellect probably has a licensing agreement with Johnson & Johnson (NYSE: JNJ) related to ANTISENILIN as well.
Commenting on the lawsuit, Daniel Chain, Ph.D., chairman and CEO of Intellect, said, "The idea that this global pharmaceutical company would attempt to withhold payment of a milestone payment stipulated in a license contract should be exceptionally distressing to every patent holder, especially small biopharmaceutical companies the size of Intellect Neurosciences, whose ability, in this case, to conduct critically important Alzheimer's research is dependent on receiving such payments from its licensees. After exhausting all non-litigious options to secure our $2 million milestone payment, we realized we have no option save pursuing payment via the courts."
The patent discloses therapeutic antibodies to treat or delay onset of Alzheimer's disease and is based on discoveries that stimulated development of monoclonal antibodies that several global pharmaceutical companies have tested as treatments for Alzheimer's disease. The antibodies specifically bind to the ends of the beta amyloid protein without binding to the amyloid precursor protein (APP), which has important advantages compared to antibodies that do not have this feature, according to Intellect's press release today. http://www.zimbio.com/The+stock+market/articles/IadrkgUEJWh/Intellect+Neurosciences+Sues+Pfizer+Over+2 http://www.bioisrael.com/daniel-chain-sues-pfizer-for-2m
ANTISENILIN® http://www.prnewswire.com/news-releases/intellect-neurosciences-receives-notice-of-allowance-from-united-states-patent-and-trademark-office-for-its-antisenilin-alzheimers-disease-immunotherapy-technology-platform-141561013.html http://www.intellectns.com/platform-technologies/antisenilin
Intellect Neurosciences Announces New Findings Supporting its Patented ANTISENILIN Platform Technology for the Treatment of Alzheimer's Disease
New Publication Demonstrates Safety and Efficacy in Reducing Brain Amyloid in Preclinical Model
NEW YORK, Nov. 28, 2012 (GLOBE NEWSWIRE) -- Intellect Neurosciences, Inc. (OTCBB:ILNS), a biopharmaceutical company engaged in the discovery and development of disease-modifying therapeutic agents for the treatment of Alzheimer's and other neurological diseases, announced today new findings on ponezumab (PF-04360365), an investigational anti-amyloid beta monoclonal antibody that specifically targets the neoepitope at the C-terminus of the peptide, published in the October 2012 edition of Current Alzheimer Research.
These new data describe the properties of a version of ponezumab in which naturally occurring sugar bound to the surface of the murine antibody was removed to improve the safety of the drug. The aglycosylated murine surrogate of ponezumab was administered by intraperitoneal injection once weekly for up to 26 weeks at doses of 0, 10, 30, or 100 mg/kg. Drug exposure and plasma amyloid beta levels increased with increasing dose. After 26 weeks, the 100mg/kg group had significantly greater plasma levels of A1-x and Ax-40 than the vehicle group (p < 0.001). There was no evidence of vasogenic edema or other drug induced pathologies.
The paper, titled, "Chronic Administration of an aglycosylated Murine Antibody of Ponezumab Does Not Worsen Microhemorrhages in Aged Tg2576 Mice," was written by Gary B. Freeman and colleagues from Pfizer Worldwide Research & Development, Groton, CT, USA.
Intellect recently was awarded a patent from the United States Patent and Trademark Office (USPTO) that discloses therapeutic antibodies that recognize the free C-terminus of A beta 1-40 to treat Alzheimer's disease.
"We are encouraged by these data supporting our belief that antibodies targeting soluble forms of A beta can be beneficial in treating AD patients. This idea is consistent with results from the solanezumab Phase 3 clinical trials, which showed a modest but consistent clinical benefit from reducing A beta monomers in the brain. That data has positive implications for the important therapeutic potential of ponezumab, as well of Intellect's internal pipeline of A beta-specific antibodies, including 1A10 (targets the C terminus of A beta at position 40), IC3 (targets the C-terminus of A beta at position 42) and 82E1 (aka IN-N01, targets the N-terminus)," stated Daniel Chain, PhD, chairman and CEO of Intellect. "We have been granted several patents by the USPTO in relation to these antibodies any of which could be developed singly or empowered with additional neuroprotective function under our CONJUMAB platform."
Intellect Neurosciences, Inc., develops innovative approaches aimed at arresting or preventing Alzheimer's disease and other neurodegenerative diseases especially focused on proteinopathies. Intellect's pipeline includes therapeutic vaccines, antibodies and neuroprotective antibody drug conjugates. For more information, please visit www.intellectns.com.
Chronic administration of an aglycosylated murine antibody of ponezumab does not worsen microhemorrhages in aged Tg2576 mice.
Pfizer Worldwide Research and Development, Groton, CT 06340, USA. Gary.B.Freeman@pfizer.com
Cerebral vasogenic edema and microhemorrhages are potential safety concerns for compounds intended to treat subjects with Alzheimer's disease (AD) by targeting amyloid β (Aβ). Ponezumab (PF-04360365) is an investigational anti-Aβ monoclonal antibody. Two hundred female mice (APP(K670N;M671L); Tg2576) 16-19 months old received an aglycosylated CHO-derived murine surrogate of ponezumab by intraperitoneal administration once weekly for up to 26 weeks at doses of 0, 10, 30, or 100 mg/kg. Drug exposure and plasma Aβ levels increased with increasing dose. After 26 weeks, the 100 mg/kg group had significantly greater plasma levels of Aβ(1-x) and Aβ(x-40) than the vehicle group (p < 0.001). Brain microhemorrhages were identified histologically using hematoxylin and eosin and/or Perls' Prussian blue iron staining. The incidence in the vehicle group was equal to or higher than those of the treated groups. There was no evidence of vasogenic edema. In summary, intraperitoneal administration of a murine surrogate of ponezumab to aged Tg2576 mice for up to 6 months did not produce any compound-related brain microhemorrhage or other pathologies.
Study Evaluating the Safety,Tolerability and Efficacy of PF-04360365 in Adults With Probable Cerebral Amyloid Angiopathy
This study is not yet open for participant recruitment.
Verified July 2013 by Pfizer
Information provided by (Responsible Party):
First received: March 4, 2013
Last updated: July 8, 2013
Last verified: July 2013
History of Changes
Estimated Enrollment: 36
Study Start Date: June 2013
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Nature Biotechnology 24, 595 - 596 (2006)
Published online: 2 June 2006 | doi:10.1038/nbt0606-595
Monoclonals expand into neural disorders
In April, Pfizer bought a Genentech spinoff, Rinat Neuroscience, for close to five hundred million dollars
Monoclonal antibodies are now being tested to treat ailments of the central nervous system, a new territory for this class of drugs.
In April, Pfizer bought a Genentech spinoff, Rinat Neuroscience, for “close to $500 million dollars,” according to one source. What drew Pfizer's interest to Rinat was its pipeline, in particular, two of its most advanced drugs. Both are monoclonal antibodies that Pfizer hopes to cash in on over the next several years. The deal demonstrates the increased interest in monoclonals in new indications, such as central nervous system (CNS) disorders.
David Pritchard, Rinat's chief business officer, says the S. San Francisco-based company offered its portfolio to eight large drug makers—and received nine offers. “The amount of interest was overwhelming,” he says, and Pfizer's offer topped the list.
Pfizer was drawn to Rinat's two top candidates. The first, coded RN624, treats pain by shutting down nerve growth factor (NGF). It demonstrated impressive early trial results in osteoarthritis patients in the third quarter of 2005 and is now in phase 2 clinical trials. RN624 drew interest because NGF “is the first new clinically validated pain target these companies have seen in decades,” points out Pritchard. The second antibody, RN1219, clears Alzheimer-causing plaque from the brains of mice, but has yet to enter human trials. “Half a billion seems a little high,” says Casey Lynch, managing partner at biotech investment advisor NeuroInsights. “But Pfizer has lots of money in the bank and their pipeline is running dry.”
Rinat's product 'is the first new clinically-validated pain target these companies have seen in decades.'
Chief Financial Officer of Rinat Neuroscience
Although only one monoclonal antibody for a CNS application (Biogen-Idec's ill-fated multiple sclerosis treatment Tysabri; natalizumab) has been approved by the US Food and Drug Administration to date, the acquisition epitomizes growing excitement in applications of biotech in the 'neuro' area. A recent analysis of 450 companies by San Francisco, California-based consultants NeuroInsights concludes that the worldwide market for neurological disease treatments was $93 million in 2005, a 7% increase over 2004. A quarter of all life sciences venture capital invested in the US now flows into firms in this area. And NeuroInsights 'neurotech' index, which tracks 30 publicly traded companies with this focus, is up 85% since 2004, whereas the NASDAQ and Standard & Poor's 500 are up just 16%.
Pfizer was interested in the quality of Rinat's pipeline, despite its early stage. Rinat's RN624 is now in a phase 2 trial in 300 patients, with full results expected in the second half of 2007. “It does appear to be first in class,” Lynch says of RN624. “It's a good application for an antibody because it targets peripheral cells. It doesn't have to cross the blood-brain barrier.”
The mechanism of action of RN624 is quite complex, however. In embryos, NGF spurs neurodevelopment. But in adults, NGF's only role, apparently, is to drive acute and chronic pain in at least three different ways. “We know it works locally—at the site of injuries and so on—and immediately increases the sensitivity of pain-sensing neurons,” says David Shelton, who began development of RN624 at Genentech in the mid-1990s and is now senior director for biology at Rinat. Second, NGF induces immune mast cells to release inflammatory proteins. Third, NGF drives a feedback loop that upregulates the synthesis of substance P and other pain-related peptides, thereby “increasing pain signaling up the spinal cord,” explains Shelton.
By binding to NGF, RN624 prevents it from latching onto nerve cells. In mouse models, this action dampens incisional, visceral, neuropathic and metastatic bone disease pain. Clinical data released in early May at the American Society of Pain meeting in San Antonio, Texas, show that RN624 effectively reduces osteoarthritis knee pain after a single injection. “It's an unbelievably clean [safety] profile,” says Shelton. “Knock on wood.”
Half a billion seems a little high, but Pfizer has lots of money in the bank and their pipeline is running dry.
As for competition, Amgen is the only other company with an anti-NGF antibody in phase 1 clinical trials. Originally developed for neuropathic pain, AG403 is now being tested against osteoarthritis pain, too. “They'll keep us on our toes,” remarks Shelton.
Rinat's Alzheimer antibody faces stiffer competition. It has yet to enter clinical trials and at least two dozen companies are also pursuing immunotherapies for Alzheimer. Most use active immunization, in which a small part of the beta-amyloid plaque is injected in hopes that it will recruit the immune system to attack disease-causing brain plaques. Rinat's RN1219 dodges the vagaries of the immune system by directly injecting an anti-plaque antibody. At least two other companies, Eli Lilly, of Indianapolis, Indiana, and the San Diego subsidiary of Elan Pharmaceuticals, of Dublin, are also pursuing so-called passive immunization against Alzheimer; both have antibodies in early clinical trials.
Elan generated a buzz in April when it released early clinical data from 30 patients receiving its monoclonal antibody bapineuzumab. The ten patients receiving the second of three doses showed statistically significant improvement in the mini-mental state examination 16 weeks after antibody injection. However, MRI scans of three of ten patients receiving the highest dose showed abnormalities that could indicate microhemorrhaging, says Dave Morgan, director of the Alzheimer research laboratory at the University of South Florida, Tampa. Morgan, who has no financial stake in Rinat or any other company, was stunned when he saw Elan's data, because he had published several articles showing small brain bleeds in mice receiving Rinat's antibody. “The human data parallels the mouse data perfectly,” he says. “When I first saw [microhemorrhaging] in my mice, I said, 'This is dead, this approach is over.' I was afraid Rinat was going to call me a lousy scientist. Instead, they wanted to see if they could correct it.”
Rinat cofounder and president, Arnon Ronsenthal, thought that a modified version of the antibody, one that didn't bind to glucose, might provide a cleaner safety profile. His team engineered such an antibody and shipped it to Morgan for mouse testing. In the May 17 issue of the Journal of Neuroscience (2006, 26 (20): 5340–5346), Morgan's team reports that the new, deglycosylated antibody clears beta-amyloid plaque as well as or better than the older antibody while causing less microhemorrhaging. The mice also performed better on a standard water-maze memory test.
Elan and others in the field are now eager to develop their own deglycosylated antibodies. But the standard method of deglycosylation uses a slow, expensive enzyme reaction. Here, Rinat has a head start—its latest antibody lacks the glucose-reaction site altogether. “They engineered it that way,” says Morgan. Citing confidentiality concerns, Rosenthal would not confirm this, but he did say that Rinat's antibody is “specifically designed to minimize” microhemorrhaging.
As for sneaking an antibody across the blood-brain barrier, no one can say for certain how the anti-Alzheimer antibodies manage the trick. Theories abound, but Rosenthal believes that, whatever, the mechanism, clinical data will drive the field. He says the company's first Alzheimer trial will begin this summer, although the company and its new owner are still debating whether to run it in Europe, Australia or the United States.
STATEMENT ON A NONPROPRIETARY NAME ADOPTED BY THE USAN COUNCIL
PRONUNCIATION poe nez' oo mab
THERAPEUTIC CLAIM Treatment of Alzheimer’s disease
1. Immunoglobulin G2, anti-(human ß-amyloid) (human-mouse monoclonal PF-04360365
clone 9TL heavy chain), disulfide with human-mouse monoclonal PF-04360365
clone 9TL light chain, dimer
2. Immunoglobulin G2, anti-(human amyloid beta A4 protein (Alzheimer disease amyloid
protein, ABPP, APPI, preA4, protease nexin-II)); humanized mouse monoclonal
PF-04360365 clone 9TL des-442-lysine(CH3107-K)-[325-serine(CH299A>S),326-
serine(CH2100P>S)]?2 heavy chain (130-219')-disulfide with humanized mouse
monoclonal PF-04360365 clone 9TL ? light chain, dimer (218-218'':219-219'':222-
MOLECULAR FORMULA C6552H10158N1730O2090S52
MOLECULAR WEIGHT 148.3 kDa
TRADEMARK None as yet
MANUFACTURER Pfizer, Inc.
CODE DESIGNATION PF-04360365, RN-1219
CAS REGISTRY NUMBER 1178862-65-1
EXCERPT - COURT DOCUMENTS 07/02/2013 MEMORANDUM OF LAW IN OPPOSITION Memo of Law in Opposition with Redactions for Efiling to Comply with Order on Sealing Motion 002 STANLEY K SHAPIRO : MEMORANDUM OF LAW OF PLAINTIFF IN OPPOSITION TO MOTION OF DEFENDANTS TO DISMISS THE COMPLAINT PURSUANT TO.CPLR 3211(a) (7) FOR FAILURE TO STATE A CAUSE OF ACTION This memorandum of law is submitted by plaintiff Intellect Neurosciences, Inc. (" Intellect") in opposition to the motion of defendants Pfizer Inc. and its wholly owned subsidiary or division Rinat Neuroscience Corp. (together "Pfizer") to dismiss the complaint pursuant to CPLR 3211 (a) (7) for purportedly failing to state a cause of action. It is clear, on fair reading of the license agreement (Agreement"), that the US Patent Milestone payment became payable upon the grant by the United States Patent and Trade Office ("USPTO") on May 8, 2012 to Intellect's of the '127 patent, granted upon a patent application listed on Schedule 1 to the Agreement (see Complaint ~~27-28). The plain and ordinary meaning and intent of the contract language, as we review below, is that the patent milestone payment is payable at the time when a Licensed Patent reaches the milestone described in the clause --that is, upon the grant in the United States of a Licensed Patent with at least one Valid Claim that covers a Licensed Product, or if the grant of US patent would have occurred in 2008 before Pfizer's exercise of the option, upon the exercise of the option. The complaint duly states a cause of action against Pfizer for breach of the Agreement by failing to make the US Patent Milestone payment after it came due upon the grant of Intellect's '127 patent --a breach of contract that is indeed established as a matter of law upon the documentary evidence and facts not in dispute. Pfizer predicates its motion to dismiss on a false assertion that the underlying contract "expressly conditions payment upon Pfizer's infringement of the patent" (Defendants' Memo of Law at 1). Yet, nowhere in the Milestone payment provision does the Agreement mention "Pfizer's infringement of the patent" or any like terms. Certainly, the Agreement does not "expressly condition" payment on "Pfizer's Infringement". Far from conditioning the Patent Milestone on there first being infringing commercial sales by Pfizer, the parties contemplated at the time the contract was made that the milestone payment would become payable on the grant of a pateilt to Intellect, even while Pfizer was still in early Phase I studies, years away from any conceivable FDA approval and commercial sales of a product. 1 When the court looks to the prior negotiations to determine what was intended, any possible doubt as to the meaning of the Milestone patent provision is removed, demonstrating conclusively that the parties contemplated and intended that the Patent Milestone would be achieved and payable even while the product was still only in Phase I study, as soon as one of the listed patents on Schedule 1 was granted in the United States --indeed even as early as the first business after January 1, 2009. The relevant negotiations are set forth and documented in the affidavit of Intellect's CFO and president Elliot Maza and plaintiff's Exhibits B to M submitted herewith in opposition to defendants' motion to dismiss, and are referred to but not repeated at length in this Memo of Law. Moreover, that the milestone payrent was intended to be due upon the grant of the patent, notwithstanding that the grant was made before any FDA approval or drug on the market is further proved by the fact that the European Patent milestone payment was actually made, "bundled" into the Exercise Fee, tv-hen the European patent was granted before the Agreement was signed, without any infringing commercial sales having been made. The evidence in context demonstrates that in reaching the Agreement, Intellect and Pfizer were guided by the payment terms of Intellect's non-exclusive license with Wyeth and Elan, entered prior to the negotiation of the subject license agreement with Pfizer, with its "most favored nation" clause. Thus, an email from Pfizer's Assistant General Counsel, Mark Cooper, dated June 12, 2008, expressed Pfizer's manifest understanding and intent that the Patent Milestone payments were to be payable upon the grant of the patent, even if granted in 2008, and not at all conditioned on there first being infringing Pfizer commercial sales. Rather, Pfizer's General Counsel staes in the email expressing the parties' intent at the time the Agreement was made that: "For clarification, the intent was [to make] the milestone payable when the Elan/Wyeth milestone is payable." (Exhibit I) (emphasis added). This intent is integrated in the final Agreement, which incorporate as Schedule 2 a Press Release, issued in conjunction with the signing that is expressly integrated into the Agreement (Exhibit A1, §1.1 at 1)2, which stated that "[r]ecently, Intellect receiv~d its first milestone payment under its license with Wyeth and Elan related to this patent family" (Agreement, Exhibit AI, Schedule 2) [referring to the analogous European Patent Milestone that was triggered by the grant a patent by the European Patent Office on July 30, 2008]. Pfizer knew there were no infringing commercial sales nor regulatory approvals yet by Elan or Wyeth of any licensed products. On its motion to dismiss, Pfize~ essentially asks the Court to rewrite the contract, to infer a condition to the Patent Milestone nowhere stated in the Agreement, that "until Pfizer infringed a newly issued Intellect patent, no milestone payment would be due" ! (Defendants' Memo of Law at 4). If ~he parties really had intended such a condition, they could easiJy and clearly have expressly stated so in the agreement that until Pfizer infringed the patent no milestone payment would be due --instead of trying to imply such a condition by resorting to the strained and specious logic artificially squeezed by implicatiqn irom isolating words out of context in the defined terms, as now argued by Pfizer. Pfizer's proposed interpretation, to infer such a material unstated condition to the obligation and time to pay the Patent milestone is further belied by Section 3.1.3[c), within the Milestone Payment section of the Agreement, which shows the intention to fully and clearly e~(press the understanding with respect to the milestone payments, repeating "[fJor the avoidance of doubt" that: "in the event that a Party has given the other Party any notice of termination of this Agreement under Article 7, no further payments under Section 3.1.3(a) shall become due following the date of such notice, but all payments due with respect to milestones achieved prior to such date shall remain payable :in accordance with their terms" (License Agreement Section 3.1. 3 [c)) (emphasis added). 4 Pfizer's motion papers also make the unfounded, evidently false representation that "Pfizer stopp~d practicing any technology covered by Intellect's patent" befor~ that patent was issued on May 8, 2012. Documentary evidence show continuing efforts by Pfizer to develop ponezumab directed to amyloid beta as a treatment for human disease, including, notably, filing in March 2013 to begin a new Phase II study (see Exhibit 0 to Maza Affidavit), as well as continued work on earlier studies (see Defendants' Exhibit 7, and Plaintiff's Exhibit N). Pfizer's continued work and interest in development ponezemab as a commercial product presumably explains why Pfizer did not exercise its right to terminate the Agreement prior to the May 2012 grant of the patent, which could have relieved it of the obligation to pay the US Patent Milestone payment had Pfizer terminated the Agreement. The documentary evidence of the negotiations, including particularly Pfizer's own proposed term sheets and drafts, put the Agreement in context to interpret the intended meaning of the Patent Milestone Provision at the time it was made, and evidence that Pfizer has wilfully and knowingly breached the Agreement. The contrived construction argued by Pfizer in support of its spurious motion to dismiss clearly does not' reflect the intention of the parties when the contract was made, and appears to be an unworthy after the fact attempt by Pfizer to rationalize its wilful default in payment, suggestive of bad faith on Pfizer's part.
part of the document 75
07/02/2013 MEMORANDUM OF LAW IN OPPOSITION - showing the perfidious argumentation of Pfizer that the due date for the milestone payment would be when they sell a product under the license terms instead of the due date clearly agreed in the license agreement:
"Licensed Product" is defined in the Agreement to "mean any product in any dosage form containing the Pfizer Compound, the development, manufacture, use, sale or importation of which product would, absent the license granted by Licensor to Licensee herein, infringe any Valid Claim in any Licensed Patent" (Agreement Section 1.11) (Complaint <J(16). By the literal terms, the definition of Licensed Product is not conditioned on there already being any commercial sales or infringement of a Licensed Product before a product constitutes a Licensed Product. Rather, any product containing a Pfizer Compound, including by definition Pfizer's Lead Compound ponezumab, is a Licensed Product if its commercial manufacture, use or sale would infJ~inge any Valid Claim in any Licensed Patent, a fact readily discernable from the plain terms of the patent (see Intellect's '127 Patent, Exhibit A4).
The complaint duly alleges that ',:he manufacture, use or sale of ponezumab to treat Alzheimer's disease would infringe at least one Valid Claim in Intellect's '127 Patent (Complaint <J(32) , an allegation which must be taken as tnle for purposes of defendants' motion. Moreover, Pfizer does not and cannot dispute that the commercial sale of ponezumab to treat Alzheimer's disease would infringe at least one Valid Claim in Intellect's '127 Patent.
Indeed, Pfizer do~s not deny th~t if it were selling Pfizer's Lead Compound ponezumab it would inf:t:inge Intellect's '127 Patent. Instead, it argues that it is not actually selling, so not infringing yet to date. But the Agr~ement's definition of License Product does not state that it is not a Licensed Product until there are actual infringing sales, but rathei that sales would infringe the patent [if there were sales].