News and Events

  • BioTecNika Magazine - Interview, Ms. Shobha Vijayaraghavan, Connexios Life Sciences

    BioTecNika Magazine, Aug 2014

    Connexios is an innovation driven, early stage drug discovery and development company focused on generating novel and highly differentiated NCEs that can be first or best in class candidates for disease areas related to metabolism, particularly Type 2 Diabetes and Non Alcoholic Steatohepatitis Fibrosis. Connexios has developed a unique Network Biology approach and platform that comprises in silico, in vitro and in vivo models of key cell types, to generate new insights into disease biology and identify novel mechanisms and targets that can be the basis of next generation therapies. This proprietary platform also includes tools for drug discovery and development, including novel assays and panels of biomarkers. Our rich and diversified pre-clinical pipeline is based on both completely original as well as recently uncovered targets, where we have been able to significantly enrich the understanding of target biology to develop Next Generation Therapies addressing the unmet needs in the selected disease areas.

    Conversing with the Vice President, Business Development, Ms. Shobha Vijayaraghavan.

    Read more:  biotecnika.uberflip.com/i/356648

  • Connexios Life Sciences and Boehringer Ingelheim Enter Agreement for Novel AMPK Activators

    Bangalore, India, and Ingelheim, Germany, May 6, 2014

    Connexios Life Sciences, a Bangalore based biotechnology company, and Boehringer Ingelheim, one of the world's leading pharmaceutical companies, today announced an exclusive global research collaboration agreement for AMPK agonists for the treatment of patients with Type 2 Diabetes.

    As part of the agreement, Boehringer Ingelheim obtains global rights to CNX-012, Connexios Life Sciences’ program on AMPK activators. The program includes CNX-570 and other compounds in early pre-clinical development. Boehringer Ingelheim will be responsible for all further development and commercialization of the candidates from the AMPK program. Further terms and financial details were not disclosed.

    "As a pure research-driven organization from India, we believe that the agreement with Boehringer Ingelheim is a big validation of both our scientific approach and capabilities as well as of our business model.", commented Suri Venkatachalam, CEO and Founder of Connexios. "CNX-012 is one of our flagship programs which leverages our Network Biology approach and platform and we are extremely pleased to be working with Boehringer Ingelheim to advance candidates from this program. We strongly believe that the collaboration will yield best-in-class activators of this exciting but challenging target and ultimately result in better therapies for patients of Type 2 Diabetes who also suffer from the burden of several other cardiometabolic co-morbidities."

    "Partnering is key to our business strategy and the partnership with Boehringer Ingelheim who have shown a strong commitment to the therapeutic area of metabolic diseases is an important milestone for Connexios. With our strengths in disease biology and drug discovery, we see great complementarity between the organizations and look forward to building on this relationship in future." added Shobha Vijayaraghavan, Vice President, Business Development of Connexios Life Sciences.

    About CNX-012 and CNX-012-570
    CNX-012-570 is the lead candidate from the Connexios program of AMPK activators that directly activate specific isoforms of the protein, designed and selected to bring about a robust impact on the cellular energetics and redox balance across key cell types and tissues. Connexios has shown beneficial outcomes from target modulation across the liver, muscle, adipose and other relevant tissues in preclinical studies across several animal models of disease. The CNX-012 program comprises several other compounds like CNX-012-570 which cover a wide chemistry and patent space.


    About Connexios Life Sciences
    Connexios Life Sciences is an early stage Drug discovery and development company powered by a unique Network Biology Platform. Connexios is pursuing several best-in-class programs at different stages of preclinical discovery and development for Metabolic disease and diseases related to NASH and Fibrosis, while also seeking to progress some of its candidates for T2DM and metabolic disorders into the clinic.

    For more information about Connexios, please visit www.connexios.com.

     

    About Boehringer Ingelheim
    The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, Boehringer Ingelheim operates globally with 142 affiliates and a total of more than 47,400 employees. The focus of the family-owned company, founded in 1885, is researching, developing, manufacturing and marketing new medications of high therapeutic value for human and veterinary medicine.

    Taking social responsibility is an important element of the corporate culture at Boehringer Ingelheim. This includes worldwide involvement in social projects, such as the initiative “Making more Health” and caring for the employees. Respect, equal opportunities and reconciling career and family form the foundation of the mutual cooperation. In everything it does, the company focuses on environmental protection and sustainability.

    In 2013, Boehringer Ingelheim achieved net sales of about 14.1 billion euros. R&D expenditure corresponds to 19.5% of its net sales.

    For more information please visit www.boehringer-ingelheim.com.

    Media Contact

    Boehringer Ingelheim

    Media & PR
    Dr Reinhard Malin
    Binger Strasse 173
    55216 Ingelheim am Rhein
    GERMANY
    Phone + 49 - 6132 – 77 90815
    Fax + 49 - 6132 – 77 6601
    email: press@boehringer-ingelheim.com


    CONNEXIOS LIFE SCIENCES

    Shobha Vijayaraghavan,
    Vice President, Business Development,
    Tel: +91-80-41210672,
    email: shobha.v@connexios.com

  • Connexios AMPK activator data published in Cardiovascular Diabetology

    Connexios AMPK activator data published in Cardiovascular Diabetology

    CNX-012-570, Connexios AMPK activator demonstrates a robust insulin sensitizer profile with significant impact on multiple metabolic parameters.

    Bangalore, India, January 27, 2014 –Data from the Connexios AMPK activator program and the lead candidate, CNX-012-570 was published online as an Original Investigation in Volume 13 of the Cardiovascular Diabetology Journal. The paper included results from PoC studies conducted with the compound in multiple animal models of disease.

    Dr. Jagannath, CSO of Connexios stated, “While we have seen clear benefits on different aspects of cardiometabolic health that are critical for the overall therapeutic profile of an anti-diabetic medicine, we are very pleased about the robust impact on the core dysregulations in Glycemic, lipid and body weight measurements. This is very important for the potential positioning of an AMPK Activator, allowing it to be introduced into the therapeutic regimen at multiple stages, for early diabetics with mainly dysregulated glucose levels as well as for advanced diabetics, where many other co-morbidities have set in and need concurrent management to reduce the overall cardiovascular risk."

    Cardiovascular Diabetology is a high impact, peer-reviewed, open access, medical journal covering the intersection of cardiology and diabetology, including genetic, experimental, clinical, pharmacological, epidemiological, molecular biology and laboratory research.

    “This is an important journal where we see a lot of cutting edge data being published on all aspects of the diabetes/cardiovascular interrelationship and the dysmetabolic syndrome and we are honoured that our paper was accepted and published in this journal. This also reflects a deep and increasing interest in AMPK as a target and as a critical therapeutic option with the potential to fulfil several needs in the clinic for T2DM and the overall metabolic disease space. We hope that we have added to this growing body of knowledge about the optimal activation of this challenging target to bring about its full impact, thereby addressing multiple core pathologies across tissues.’, added Dr. Suri Venkatachalam, CEO, Connexios.

    About CNX-012-570

    CNX-012-570 is the Lead candidate from the Connexios program of AMPK activators that directly activate specific isoforms of the protein, designed and selected to bring about a robust impact on the cellular energetics and redox balance across key cell types and tissues. The data included results that confirm target modulation by CNX-012-570 across the liver, muscle, adipose, endothelium and macrophage and other relevant tissues, and corroborate previously articulated hypotheses about the target MoA underpinning the physiological outcomes in preclinical studies.

    About Connexios

    Connexios Life Sciences is an early stage Drug discovery and development company powered by a unique Network Biology Platform. Our portfolio comprises several best-in-class programs at different stages of preclinical discovery and development for Metabolic disease and diseases related to Fibrosis, including Chronic Liver and Kidney disease.

    For further information about CNX-012-570 and Connexios programs, please contact:

    Shobha Vijayaraghavan

    Vice-President, Business Development

    Connexios Life Sciences

    shobha.v@connexios.com

    Tel: +919845946966

  • Connexios Lead Candidate, CNX-013-B2 on track to enter IND enabling studies in 2014

    CONNEXIOS LEAD CANDIDATE, CNX-013-B2 ON TRACK TO ENTER IND ENABLING STUDIES IN 2014


    Keystone Symposium, Vancouver, 15th January, 2014.– Connexios Life Sciences announced that its lead candidate CNX-013-B2 is on track to enter IND enabling studies under GLP conditions in 2014. During 2013, the Company systematically executed on key activities required for initiation of the GLP studies, including PoC in multiple animal models and long-term safety studies. Throughout the preclinical program, CNX-013-B2 has demonstrated robust efficacy across multiple parameters with a clean safety profile.

    "The emerging data on CNX-013-B2 confirms its potential as a novel therapy to impact outcomes associated with Metabolic Syndrome, T2DM and Dyslipidemia. The profile of the lead candidate could fulfill a deeply felt clinical need to modulate multiple parameters and consequently impact residual cardiovascular risk in patients with Type 2 Diabetes Mellitus and/or Dyslipidemia. Extensive preclinical data have been generated with this compound and substantial work has been done to define its risk-benefit status. If this preclinical data translates into positive outcomes in the clinic, the molecule has the potential to be an important addition to the therapeutic armamentarium for the management of patients with Type 2 Diabetes and Dyslipidemia” noted Dr Sreeharan, MD, PhD, Senior Partner, Transcrip Partners, Former SVP and European Medical Director, GSK Ltd., Visiting Professor, Post Graduate Medical School, University of Surrey and a member of Connexios' Scientific Advisory Board.

    The effect on the different parameters was significantly superior to that shown previously with other agents in the class. In multiple well recognized animal models designed to study the effects on T2 Diabetes, Dyslipidemia and Obesity, CNX-013-B2 showed a robust reduction of >21% PPG, >25% LDL-C and 10% in body weight gain. In addition, the lead compound showed a significant impact on Muscle endurance resulting in improved ability to exercise.

    "While several well-known groups and companies have worked on these critical mechanisms, the outcomes have remained elusive, with many programs being discontinued due to lack of efficacy or safety. On the other hand, we have spent a significant part of our efforts in understanding the molecular mechanisms underlying the target biology in great detail so as to create a rigorous screening strategy to select candidates that bring out the full potential of the target and therefore likely to be best-in-class. As a potent agonist of Retinoid X Receptor isoforms α, β and γ CNX-013-B2 transactivates the three PPAR isoforms α, β and γ but yet does not carry any of the safety risks associated with these nuclear receptor targets that have plagued many of the previous programs.” said Dr. Jagannath, CSO of Connexios.

    “We are extremely excited about the clinical and commercial potential unfolding around this target and our compound as it clears hurdle after hurdle in the course of development. Each of the indications addressed by CNX-013-B2 represents a large patient population with significant disease burden. It appears that therapies like these could provide real hope for patients who are doomed to see secondary failure over time and have to keep increasing the pill burden, while slipping on the primary goals of treatment." mentioned Dr. Suri Venkatachalam, CEO of Connexios.

    About CNX-013-B2

    CNX-013-B2 is the Lead candidate from the Connexios RXR agonist program and fulfills the TPP of a Next Generation Anti-diabetic, demonstrating significant impact on multiple metabolic parameters including robust control of Hyperglycemia, Hypertriglyceridemeia, Hypercholsterolemia and Obesity. In addition, the candidates have also shown a direct and clinically relevant impact on Cardiovascular health as well as Exercise mimetic effects thereby demonstrating the potential to provide multiple therapeutic benefits in the clinic for the several co-morbidities affecting a typical Type 2 Diabetic patient.

    Connexios Life Sciences is an early stage Drug discovery and development company powered by a unique Network Biology Platform. Our portfolio comprises several best-in-class programs at different stages of preclinical discovery and development for Metabolic disease and disease related to Fibrosis, including Chronic Liver and Kidney disease.

    For further information on the CNX-013-B2 program and Connexios, please contact:

    Shobha Vijayaraghavan

    Vice-President, Business Development

    Connexios Life Sciences

    shobha.v@connexios.com

    Tel: +919845946966

  • Infosys founder NS Raghavan's venture investing arm invests Rs 100 crore in Connexios

    Infosys founder NS Raghavan's venture investing arm invests Rs 100 crore in Connexios

    ET Bureau, Apr 13, 2012

    In 2003, Nadathur Holdings, the venture investing arm of Infosys co-founder NS Raghavan, made its first investment in Connexios, a small drug discovery startup in Bangalore. Nadathur has since pumped in Rs 100 crore, by far the largest investment in an Indian drug discovery company.

    Nine years after the first investment, Connexios, founded by scientist Suri Venkatachalam, is yet to generate its first rupee in revenues. But Nadathur is now readying the next tranche of investment - a few million dollars more at the least.
    What's so special about Connexios? And why is Nadathur Holdings backing it big time?

    Connexios does what larger pharma companies with diverse revenue streams and bigger balance sheets have struggled to do - develop a new drug from scratch.
    It now has an anti-diabetes molecule, called CNX-011-67, which has crossed animal trials. It also has a few others entering pre-clinical development.

    Connexios is looking for a big company to license CNX-011-67. If successful, it could net a few million dollars. A few more big licensing deals may follow in the near term.
    And yet, such is the risk of drug discovery that if there are no takers, Connexios may have a long and tortuous journey ahead.

    Failure is common even in US, Europe

    Failure is common in this domain even in experienced environments in the US and Europe.
    "It is an incredible achievement to have sustained such high levels of investment in an Indian drug discovery company," says Nitin Deshmukh, CEO of Kotak Private Equity. "We knew when we funded the company that we had to support it for the long term," says Sriram Nadathur, a director of Nadathur Holdings and Raghavan's son.

    Nadathur is not a novice. It has so far invested $600 million in 25 startups in India. About $50 million is in life sciences companies.
    Nadathur's big investment has enabled Connexios build a large team: 190 people, including 130 scientists. No startup in the US or Europe at this stage of development can afford to have so many scientists. Since Connexios is focused exclusively on Type II diabetes and related diseases, the large scientific team provides it with enormous depth in one area.

    "I was surprised by Connexios," says its London-based non-executive chairman Rolf Stahel. "It has this incredibly detailed approach to one disease area, which increases its chance of success enormously."
    Stahel is a 30-year industry veteran, whose latest achievement was to take the 50-employee, $3-million Shire Pharmaceuticals to an 1,800-employee $1.1-billion company ranked 86th on FTSE within nine years.

    Indian pharma companies began drug discovery in the early 1990s, but haven't yet launched a single drug.
    Many have reduced such research, and Dr Reddys has exited the activity altogether as the risks and expenses were too high. Venture capital firms also baulk at funding pure play drug discovery firms because of the risks involved.
     

    However, drug discovery services companies such as Advinus and Syngene have flourished as big pharma started outsourcing to India. Some of them are trying a servicescum-product business model.
    Connexios has stayed away from services and does only new drug discovery.

    It remains a unique company in the world because one investor has decided to fund the company till it no longer needs funding. "We did not invest in Connexios like an angel investor or a venture capitalist," says Sriram Nadathur. "Suppose we invested as an angel. Who would you go to for the second round?"
    When Connexios started in 2003, both Venkatachalam and Nadathur wanted to develop knowledge in network biology. "We then invested in ideas. There were no business plans," says Sriram. Having developed some knowledge in terms of biochemical network databases within a few years, the path ahead was not clear. "We were not sure of the need for these databases," says Venkatachalam. Connexios then started using the databases to develop assays — jargon for methods to find out how well a drug target works.

    "We thought we could license both the assays and the databases." Things were still not very clear after it developed some assays. In 2008, the founders and Sriram sat together to decide the future course. It was to be drug discovery. Connexios then had about 20 people.
    It expanded rapidly with facilities for biology, drug discovery and animal testing. It also decided to focus on metabolic disorders such as Type II diabetes. Its scientific workforce expanded to 130, including 30 PhDs. "We do not have the ecosystem to outsource work," says Sriram, "and so we needed to do everything in-house."
     

    When it began, Connexios had no clue about drug discovery. It focused on diabetes because it was a complex disease that required a network approach but the market was big as well.
    The diabetes drug market is set to expand from $34.9 billion in 2010 to $48 billion in 2015, according to IMS Health. And yet, diabetes drug discovery is becoming more difficult as the regulators have become more stringent.

  • Connexios in discussions to partner early-stage GPR40 diabetes drug, CRO will be chosen in US/EU – CEO

    Connexios in discussions to partner early-stage GPR40 diabetes drug, CRO will be chosen in US/EU – CEO

    Riddhima Saxena and Mai Mizuta, Merger Markets, London, Apr 10, 2012

    Connexios Life Sciences, a private Bangalore, India-based, drug discovery company is in talks with European and US pharmas regarding partnership opportunities for its lead compound CNX-011-67, a GPR40 antagonist for the treatment of Type II diabetes, CEO Suri Venkatachalam said.

    A clinical research organization (CRO) will be chosen either in the US or Europe, after proof of efficacy trials, a company source said. The compound is set to go into Phase I trials in July 2012, he added.

    The deal could be structured either by out-licensing the candidate to a major pharmaceutical firm or getting a financial or mid-sized strategic investor, Venkatachalam said. In the latter scenario, the strategic investor could infuse funds and later out-license the compound to a larger player for late-stage development and commercialization, he added.

    The company is interested in discussions with pharmaceutical companies and advisors on potential partnership opportunities, the CEO said. Early-stage deals are better carried out internally, while engaging advisors is more prudent for late-stage deals, he noted. Connexios has a UK-based legal firm for due diligence, he said.
     

    Deal value would be consistent with similar anti-diabetes drug programs, the CEO noted. California-based Exelixis (NASDAQ:EXEL) out-licensed its TGR5 agonist program, an early stage diabetes drug, to Bristol-Myers Squibb (NYSE:BMY) for USD 250m. Connexios hopes to receive cash through partnering deals rather than private equity funding, the CEO noted.

    The company is also interested to speak with Japanese pharma companies regarding partnering opportunities, he added.

    Takeda (TYO:4502) is also spearheading the development of GPR40 agonists, as previously reported by this news service. The Japanese company’s drug is in Phase III and is two to three years away from commercialization, while Connexios’s is five to six years away from commercialization, he noted.

    Amgen (NASDAQ: AMGN) was developing a clinical GPR40 agonist candidate AMG-837, but this news service reported in January 2012 that the drug had been discontinued due to safety signals.

    Established in 2003, Connexios has one investor, and is funded by private equity firm Nadathur Holdings and Investments, a life science fund. The source noted that the fund had invested into the company with a long-term view, but he acknowledged an exit strategy could come within the next five years. “It is too early right now for M&A,” the source noted.
     

  • Connexios presented data on a novel GPR40 agonist, CNX-011-67 at the 71st Scientific Sessions of the American Diabetes Association meeting in San Diego, CA, June 24-28, 2011

    Connexios presented data on a novel GPR40 agonist, CNX-011-67 at the 71st Scientific Sessions of the American Diabetes Association meeting in San Diego, CA, June 24-28, 2011

    Jun 24, 2011

    GPR40 is a G-protein receptor coupled mainly with Gαq11, which activates phospholipase C resulting in the production of IP3 and DAG. In humans, GPR40 is expressed mainly in the pancreas, brain and macrophages. GPR40 is reported to play an important role in glucose and fat-mediated insulin secretion. It is now established that GPR40 does not mediate lipotoxicity. Activation of GPR40 by small molecule is reported to enhance insulin secretion.

    We report development and application of a highly selective, potent and safe GPR40 agonist, CNX-011-67, which exhibits unique properties to improve β cell function under conditions of metabolic stress. CNX-011-67 improves glucose selectivity of β cells and enhances glucose-stimulated insulin secretion and content in multiple species including human T2DM islets. In a preclinical model of T2DM, CNX-011-67 has demonstrated good anti-diabetic activity.
     

  • Vantage Point - Indian scientists on quest for country's first novel molecule

    Vantage Point - Indian scientists on quest for country's first novel molecule

    EP Vantage, Nov 02, 2010

    If India’s presence in the world of generic drugs is well established, its efforts to gain a foothold in the field of novel medicines are still very much a work in progress - an Indian-discovered new molecule has yet to receive marketing approval anywhere in the world.

    The desire to see this happen is widely held by the country’s researchers, more and more of whom are being employed in the search for just this in labs of both foreign and domestic companies. It is no doubt only a matter of time and many are predicting significant advances in the next five years, although it appears unlikely that a truly novel agent will make it to a Western market in this time frame. Still, when the first approval happens the event will certainly represent a significant stride up the value chain for India’s pharmaceutical industry.

    Vast Knowledge

    With vast knowledge of small molecule manufacture and chemistry gained from years of copying novel compounds derived elsewhere, India’s generic drug developers have been applying this knowledge to new discoveries for some time. This includes most of the established Indian drug developers like Glenmark Pharmaceuticals, Zydus Cadila and Lupin, which have been active in this space for around a decade.

    Small start ups are also now emerging; Connexios Life Sciences and Incozen Therapeutics a couple of recent examples.

    Considering it can take 15 years for a new molecule to reach the market, it is perhaps not surprising that these efforts have yet to generate a success story. A few molecules have made it into later stage development and there are increasing numbers approaching this stage, but the final regulatory barrier has yet to be breached, either within India or beyond.

    “India is growing strongly in drug development and will make a major foray in the next five years in new chemical entities,” predicts Sham Nikam, vice president of global discovery for Nycomed (EP Vantage Interview - Nycomed planting deep roots in India, November 2, 2010).

    The ever growing number of Indian companies taking this goal seriously means this prediction could well come true. And in a sign of growing activity and interest, Bio, the world’s largest biotechnology trade organisation, held its first partnering conference in India this year.

    Others, however, are more circumspect, particularly when it comes to succeeding in getting a novel product approved in the US or Europe.

    “In Indian markets it will perhaps take five years, but in the regulated markets it might take more,” says Chirag Talati, pharma analyst for Execution Noble.

    Much of the really novel work on interesting targets, which would be more attractive to take to Western markets, is still very early stage, he says.

    Shifting mindsets

    Innovation comes on a sliding scale and most Indian research is being conducted into well characterised modes of action – a lower risk strategy certainly not restricted to this region. This prompts a certain amount of criticism of the country’s pipeline, as being heavily focused on lower value, “me-too” molecules, but there are definitely signs that Indian research is becoming more ambitious.

    Glenmark, for example, was one of the first Indian firms to invest in novel research and has gradually become much more ambitious, says Dr Neelima Joshi, vice president of the company’s R&D operations.

    Initially when we got into drug discovery nine years ago we were exclusively working on clinically proven targets, there would be molecules well ahead of us in late stage, with data on safety and efficacy, so we would have benchmark compounds to compare.

    “Based on that we gained a lot of internal knowledge and subsequently moved into less explored targets, where there was some literature and information on biology and chemistry, but nothing in clinical development. Now we are exploring totally unprecedented targets where there is nothing in pre-clinical stage,” she says.

    This strategy has helped Glenmark successfully find partners for compounds emerging from its research labs, most recently with Sanofi-Aventis. Earlier this year the French pharma giant bought rights to its vanilloid receptor antagonist programme, for chronic pain, in a deal worth up to $325m. The most advanced candidate is in phase I.

    Dr Joshi says that the five deals the company has struck over novel molecules during the last decade has brought in $140m. Based outside Mumbai, the firm’s state-of-the art facility employs 200 scientists conducting all aspects of pre-clinical work, a significant scale of activity that has been enthusiastically backed by Glenmark’s chief executive and founder, Glenn Saldanha.
     

    Natural progression

    No other Indian firm has managed to out-license as successfully as Glenmark, but pipelines and potential are building.

    Zydus Cadila, for example, has a pipeline of eight clinical candidates, the most advanced is in phase III trials in dyslipidaemia, a PPAR alpha-gamma agonist called ZYH1. The company is focusing on metabolic disorders and pain and, like Glenmark, has no plans as yet to take these products to external markets itself, aiming to partner at a late stage of development.

    Pankaj Patel, Zydus Cadila’s chairman and managing director, agrees that getting an Indian-discovered medicine to market will bring recognition, but says quality is still important.

    “Obviously for any pharmaceutical company the goal ultimately is to sell its own products, it’s a dream, and we think we can become a fully integrated pharmaceutical company,” he says. “But my objective is not to be first but to be the company who has a significant product,” he says.

    Dr Kamal K. Sharma, managing director of Lupin, another traditionally generic firm investing in novel R&D, describes this move as “natural progression”.

    “If we are a technologically strong company, then it’s natural progression to move up the value chain. You are strong in organic synthesis, then you are strong in formulation development, then formulation technology and delivery, then the logical end is new chemical entities,” he says.

    Perhaps the best example of this move up the value chain can be seen at Piramal Healthcare, which earlier this year sold its core branded generics business to Abbott Laboratories for a huge $2.12bn upfront. The stand alone Piramal Life Sciences is now a pure R&D outfit, boasting several phase II candidates in oncology, inflammation and anti-infectives and deals with Eli Lilly and Merck $ Co.

    The asymmetry of this deal – an Indian generics giant focusing on innovation by selling its commodity business to a traditional brand-focused Western healthcare company – neatly encapsulates two distinct global strategies, and it will be interesting to see if they both bear fruit.

    Novelty still in its infancy

    At the same time as India’s traditional generics players are dipping a toe in the R&D world, the country is also seeing more start-ups. And here some of the really innovative work is going on.

    Bangalore-based Connexios, for example, has developed a translational network biology platform to help it identify new targets in metabolic diseases, and their small molecule modulators. The company is also working on existing targets, and it is likely to reveal more details on its lead candidate shortly, a GPR 40 agonist. Few are working on this target; only Takeda has a candidate in the clinic, according to Suri Venkatachalam, chief executive and founder.

    He says the company is working on filing an IND in the US, but wants to find a partner to take the compound into the clinic. This would bring in some non-dilutive funds to the company, which has so far been backed by an investment firm, Nadathur Holdings.

    Mr Venkatachalam is optimistic that India’s time in novel medicines is coming, but also acknowledges that work has only really just begun.

    “Companies are only now beginning to commit resources to really novel R&D,” he says. “It will be tough for many Indian organisations to change the mindset from generics and contract-lead research to proprietary novel research.”

    Big challenges no doubt remain, not least the lack of structures in place that encourage the type of early stage entrepreneurship and innovation seen in the US and Europe. Mr Talati of Execution Noble agrees that the industry is still really in its infancy in India.

    “We are seeing an increase in activity, but I can’t say it is growing by leaps and bounds. There are quite a few issues, there are no systems in place where Indian academia can develop something and then license it to industry, and the culture of innovation in academia is not really present,” he says.

    On top of this, finding funding is tough, with few Indian venture capital firms willing to invest in early stage, high risk drug development.

    All of which means the first Indian-discovered new chemical entity to reach patients is unlikely to represent a huge medical breakthrough, and it could well be launched outside the really lucrative markets of Europe and the US. But progress is being made at all levels of innovation, and the country’s journey up the small molecule value chain is gathering momentum.
     

  • Young Turks – Ideas Without Boundaries (Pharma Special)

    Young Turks – Ideas Without Boundaries (Pharma Special)

    CNBC TV18, July 16, 2010

    Suri Venkatachalam of Connexios, a biotech firm that focuses on the discovery and development of proprietary drug molecules. Starting with just 9 researchers and Rs 10 lakh the team of scientists at Connexios has connected the dots to develop strains to treat diseases like Type 2 Diabetes Mellitus, Obesity and Liver Disorders. Though a nascent business in India, Suri sees drug discovery the next growth driver for the industry. 7 year of intense research and investments of over Rs 50 Cr into the venture today, Connexios is closing in on its first big deal for its composition in diabetes.

  • Connexios: Harnessing the Indian cost advantage in network biology

    Connexios: Harnessing the Indian cost advantage in network biology

    Eleanor Malone, Jun 01, 2010

    Imagine if a start-up company could afford to hire enough high-calibre scientists to spend years creating a detailed map of a broad and complex pathology like metabolic disease, incorporating large amounts of cellular and molecular biological data, into which it could plug further swathes of clinical information. Imagine if it was then able to evaluate existing drug R&D against this map, and identify promising areas for potential future drug discovery and development, which it would then proceed to carry out itself. All with the financial backing of an enthusiastic private investor. It seems unlikely, but this is precisely what Connexios Life Sciences has done. Scrip's companies editor Eleanor Malone met CEO Dr Suri Venkatachalam to find out more.

    Connexios Life Sciences is an unusual company in more ways than one. Established in 2003 and based in Bangalore, it is unusual in India in that it is a drug discovery-focused biotech firm looking to create its own intellectual property that will be of global value. This international outlook is reflected in its board of directors and scientific advisors, which includes among others Dr Colin Greengrass, Pfizer's former director of strategic alliances, Professor Rohit Kulkarni of the Joslin Diabetes Center at Harvard University, Dr Lily Chan, former CEO of Singapore's S*Bio, and, its latest recruitment coup, non-executive chairman Rolf Stahel, former CEO of Shire Pharmaceuticals.

    Dr Suri Venkatachalam, CEO of Connexios Life Sciences

    It is also unusual in the international biotech community in that it has taken a very broad, comprehensive approach right from the start, rather than building up around a single specialist technology, type of drug target or candidate or skill set.

    Commenting on Connexios's status as a biotech firm in a country whose economy is driven largely by trade and cost-arbitrage businesses - retail, IT services, telecommunications and so on - founder and CEO Dr Suri Venkatachalam observed: "In an economy that is growing at about 8.5-9%, there's so much low-hanging fruit that people don't want to invest in a seven-year gestation period."

    But while biotech innovation might seem like an unnecessary risk for most domestic investors, from a global point of view, India makes a lot of sense as a venue. The country has a tradition of creating good scientists, many of whom have studied and worked abroad. However, salaries and other overheads are a fraction of those in the developed markets. Many big pharma firms, recognising this, are expanding operations in the country, even if home-grown start-ups are thin on the ground.

    In fact, it is these factors - low cost and strong talent - that have been key to Dr Venkatachalam being able to pursue his ambitious venture to build a drug discovery engine based on a broad and thorough understanding of the range of mechanisms involved in metabolic disease. The third element in Connexios's success to date has been the unusual enthusiasm for long-term investment in life sciences enterprises of its financial backer, Nadathur Holdings and Investments (the investment vehicle of the high net worth family of NS Raghavan, one of the co-founders of the Indian IT services giant Infosys).

    the approach

    In the early years Connexios focused on building its platform, and did not have a clear plan to use this for internal drug discovery. This may seem short-sighted, but Dr Venkatachalam described his company's approach as "agnostic", and it is clear that what Connexios lacked in terms of long-term business plan, it more than made up for in the breadth of its vision. Not content to focus on a single piece or even a section of a large jigsaw, it wanted to build a clear picture of the entire jigsaw before it decided what to home in on.

    "The basic scientific foundation for the approach is that you need to look at disease in a much more systematic way and not just look at it in a target-centric way. Historically, I think the way the pharma industry has acted is really to look at drugs from a very target-centric approach and then engage with the biology which is around the target. We've tried to flip that round a bit to look at the disease first, the key mechanisms which underlie the pathology at the cellular and molecular level, in a much more integrative fashion, and then try to locate targets within it," explained Dr.Venkatachalam.

    The disease area the firm has chosen, metabolic disorders, is a particularly complicated one.
     

    "Metabolic disease is a classic case for this approach, because it's a systemic disorder, it involves multi-factorial knowledge and multiple tissues: it's begging for an integrative systems kind of an approach," explained Dr Venkatachalam. "Traditionally, this is an area where very little integration has been done. People have focused on HbA1cs, glucose excursions, and so on, but we say that's the tip of the iceberg: what's really going on is a lot of complex biology in multiple tissues." Also attracting Dr Venkatachalam and his team to metabolic disease was the fact that it is such a large and growing disorder, with India now, in his words, the "diabetic capital of the world".

    "To put together a team like this would have been a financial nightmare in the US or Europe"

    Plenty of small companies would probably like to be able to take this kind of a measured, rational approach, starting broad and homing in on promising leads later: but available resources dictate that they keep their focus fairly narrow right from the start. This is where Connexios was able to leverage the "Indian advantage".

    "We've managed to put together a team at fraction of the cost [a company in developed markets would face]. We have about 120 scientists and close to 30 PhDs in the company, many of them with experience abroad. To put together a team like this would have been a financial nightmare for a company trying to start in the US and Europe. You couldn't do it. But because of the cost structures in India, until about two and half years ago when we started full-fledged drug discovery, we were spending a pittance every year," the CEO said.
     

  • Stahel sees scale in India

    Stahel sees scale in India

    BioCentury, Apr 12, 2010

    By Stephen Hansen, Staff Writer

    Indian biotech Connexios Life Sciences Pvt. Ltd. is hoping to pattern itself after Western R&D-focused biotechs by building a pipeline of compounds against novel targets backed by a strong understanding of disease biology. The scale of the company’s research team has attracted Rolf Stahel as non-executive chairman to add international business development and marketing acumen to the science that is already in development.

    Like other small biotechs, Connexios hopes to fill the gap at pharma companies such as AstraZeneca plc that have become more dependent upon in-licensing to offset cuts in their own discovery research (see BioCentury, March 15).

    Developing relationships with pharma and big biotech is where Stahel will play a role. Stahel became CEO of Shire plc in 1994 following 27 years at Burroughs Wellcome Co. (now GlaxoSmithKline plc). At the time, Shire had 15 employees and about $1 million in revenue, with a valuation of around $30 million. When he left in 2003, Shire had annual revenues exceeding $1.2 billion, more than 1,800 employees and a $4.8 billion market cap.

    After leaving Shire, Stahel didn’t want to start over building another company. Instead, he decided to accept a limited number of offers to serve as non-executive chairman.

    “As non-executive chairman, I can focus on transferring the knowledge that I gained at Wellcome in terms of marketing and the interaction of marketing and R&D, and the knowledge I gained at Shire of it being a tiny company and bringing it to the FTSE 100. I thought that knowledge could be valuable to smaller companies that are perhaps less business-oriented but strong in science,” Stahel told BioCentury.
    Stahel is non-executive chairman of neurology company Newron Pharmaceuticals S.p.A., drug delivery company Cosmo Pharmaceuticals S.p.A. and cancer and neurology company EUSA Pharma Inc.

    Connexios was founded in 2003 to develop small molecules for diabetes and related metabolic disorders. Stahel said at first he was skeptical that a small company could be doing innovative science in a developing country like India. What changed his mind was the company’s approach to R&D spending.

    Connexios takes advantage of the low cost of high quality scientists in India, which Stahel put at 10% of Western salaries, and “instead of saving the money, they spend about the same amount of money that we would in a biotech company in the West, but they increase the number of scientists employed tenfold, which allows them to take a very detailed approach to a limited field,” he said.

    The company hasn’t disclosed how much it spends on R&D, but 130 of the about 170 employees are scientists. This is “a very rich set of employees” compared to most startup or small cap biotechs, Stahel said.

    The biotech has used this headcount to research the detailed pathophysiology underlying disease.
     

    “Our network biology approach has allowed us to articu-late all the key pathways that are critical in linking the targets to their physiological impact and hence their clinical relevance,” CEO Suri Venkatachalam told BioCentury.

    “If you have 30 biologists working for three years on nothing else but studying the disease in every relevant organ of the body, then you know their approach is very serious,” Stahel said.

    The company’s lead compound is CNX-011-326, an agonist of free fatty acid receptor1 (FFAR1; GPR40). It is in preclinical development for Type II diabetes. The company also has 11beta-hydroxysteroid dehydrogenase type 1 (11b HSD1) inhibitor in preclinical development for the indication.

    Connexios has disclosed two other programs in discovery for Type II diabetes: AMP-activated protein kinase (AMPK) activators and retinoid X receptor (RXR) activators. RXR modulators are used to treat cancer, such as Targretin bexarotene from Eisai Co. Ltd., which is approved to treat cutaneous T cell lymphoma (CTCL). Venkatachalam said he isn’t aware of any other programs focused on RXR as a target for diabetes.

    Connexios also is validating undisclosed targets for metabolic disorders. “We are reasonably sure that there aren’t any active drug discovery programs on these targets. We hope to disclose some of these targets in the coming months,” Venkatachalam said.
     

    Stahel said Connexios hopes to have 5-10 projects under development within two or three years and will seek to outlicense them in preclinical or early clinical development. He hopes Connexios will announce its first out-licensing deal within the next 12 months.

    “Ultimately, maybe even this company will try to keep one or two projects in-house so that would then lead toward a company that maybe 15 years from now might have its own marketing organization. But that’s a long shot,” Stahel said.

    Connexios is developing its compounds for a global market and will pursue IP protection on a global scale.

    The biotech has raised an undisclosed amount of money from its sole investor, Nadathur Holdings and Investments, an investment firm for the N.S. Raghavan family in Bangalore.

    Stahel said Nadathur has a long-term vision for building the company, but “it may not be a bad idea to invite a high quality international VC to join the party, simply because of the network they bring. These are options that over the next two to three years the company will regularly review.”
     

  • Connexios Aspires to Become the 'Jewel' of India's Biotechs

    Connexios Aspires to Become the 'Jewel' of India's Biotechs

    BioWorld International Mar 24, 2010

    BioWorld International Correspondent

    LONDON - The former CEO of Shire Pharmaceuticals Group plc, Rolf Stahel, has become nonexecutive chairman of an Indian drug discovery and development specialist Connexios Life Sciences Pvt Ltd, a move he said reflects a step change in the maturity of the biotech sector in that country, which is moving from providing services and being the junior partner in collaborations, to doing discovery and development on its own behalf. That advancing maturity should serve also as a "warning sign to politicians" in the UK and the rest of Europe, Stahel told BioWorld International, adding that he is "disgusted at their relative inactivity in defending [the industry]." One of the most significant advantages that India has in building its biotech sector is the ready supply of highly qualified scientists, who command salaries that are 90 percent lower than in the West. "There's no difference in quality so [small biotechs] have the advantage that they can afford to get big numbers of scientists involved to do a more thorough job," Stahel said. In the case of Connexios, a specialist in metabolic disorders, 30 biologists have devoted three years to the exclusive study of diabetes. That has yielded a pipeline of novel small molecules that are now approaching clinical development. They include, CNX010, which acts to reduce hepatic glucose output; CNX011, which improves glucose-stimulated insulin secretion; CNXFC010, a combination treatment that reduces the accumulation of fat in the liver and improves the uptake of glucose by muscles, among other effects; CNX013, which enhances adipocyte insulin sensitivity and secretion; CNX016 that acts by mobilizing and oxidizing fat, increasing insulin sensitivity; and CNX017, which reduces hepatic glucose outp

    This looks exciting to me, but the ultimate proof is when [Connexios] does the first deal with pharma," Stahel said. Connexios' compounds were generated through a proprietary platform that integrates systems biology approaches with high-throughput screening and biomarker and assay development. The company also has an in-house medicinal and computational chemistry team for taking hits forward. Connexios contended that its underlying biological knowledge enables it to develop assays and prognostic biomarkers that will speed progress in discovery and development. The company plans to find licensing partners for investigational new drug-ready molecules and associated biomarkers for clinical development and commercialization. It is also looking for broader collaborations for the "joint exploitation" of its portfolio of targets and its discovery platform. With the appointment of Stahel, who took Shire from revenues of $30 million to revenues of $1.1 billion in his nine-year tenure, Bangalore-based Connexios is starting to build its profile outside India. The company's founder and CEO Suri Venkatachalam said, "2010 is going to be a significant year for us as we initiate clinical development with our discovery portfolio." While India derives a huge competitive advantage from arbitraging its low-cost labor force, it lacks another resource crucial to growing a biotech sector, having a poorly developed angel and venture capital investor base. Stahel said one of the reasons he was attracted to Connexios is the fact it has one very supportive private investor, Nadathur Holdings and Investments Pvt Ltd. Nadathur is an investment firm set up by N S Raghavan, the founder of Infosys, after he retired from the Indian information technology services specialist in 2000.

    Nadathur's goal is to promote entrepreneurship in India, funding start-ups in life sciences, information technology and engineering, and the firm now has 17 companies in its portfolio. Venkatachalam founded Connexios in 2003, having previously set up another Nadathur-funded company, Metahelix, which specializes in the development of genetically engineered crop plants. Stahel said his duties as nonexecutive chairman of Connexios could cover &anything but the science.& That is likely to include an international approach to financing, strategy, business development and merger and acquisition activity. &The company is keen to become the jewel of biotech in India. "This is a sign of the maturing of biotech in the country as a whole,& Stahel said.