Big Idea 2015: Haute Apothicaire

There are medicines & then there is Haute Apothicaire

From what’s written on the wall, 2015 could well be the year when good old medicine finally goes designer chic. Even if not for the masses just yet, a privileged few could soon have their meds custom made to match their genes - well, just as soon as the fitting trials are done & the master says aye!

For those who didn't quite get my pun, I am indeed talking about personalized medicine going mainstream in 2015 - From Novartis making the first move to bring protocol to patient through its series of #SIGNATURE trials & JnJ opening up its clinical data vaults to Yale for open research to #Google #Calico aiming to tackleageing through big data & bigger collaborations, it's clear there's this huge trend of big pharma going all guns blazing after the alluring promise of personalized medicine.

This alliance with big data is in some way an existential manoeuvre by big pharma poised precariously on the patent-cliff & thus most initial approvals of designer drugs would be those that have been pulled up from the gorges of failed/failing PII/ PIII trials. Either which way, there is no doubt that the best use of cutting-edge drug design capability is only when it is coupled with the invaluable human genomic & proteomic data decoded in the past decade and using the #bigdata analytics to throw up the statistically best therapeutic match for an individual patient.

If one goes by the regularity with which FDA has been approving companion diagnostics and genetic tests over past few years; the apparent merit they see in the label of an approved drug referencing the genomic biomarker(s) & the pragmatic use of conditional approvals such as the recent one for Translarna by the EMA, it appears the regulators too are in sync with this new reality & have been gearing upto deal with the potential multitudes of personalized therapeutic applications & evolve an approval mechanism that's applicable despite the indication not being orphan enough.

Even as connoisseurs may not quite like it, high fashion attains scale only when it goes mainstream & by analogy the designer drugs too would find their way to the masses eventually, I only hope sooner & safer.

#BigIdeas2015 #Google #Calico #Bigdata

Is YODA-enabled clinical data-transparency more than smart externalization of clinical data-mining & analysis?

The day started with a news item on Xconomy declaring "J&JOpens Data Vault to Yale, in ‘Unprecedented’ Transparency Move" - Surely an important development on something that's been propounded for long - below is my comment on this piece;

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Way back in March 2008 a fellow member initiated a discussion topic titled ”Radical Transparency for Drug Safety?” on Pharmaceutical Discussion Group that I manage. The brief engagement that this topic generated ended up identifying the following as ‘key aspects that need to be addressed’ before radical transparency becomes acceptable to pharma;

• Enabling climate (safe harbor) &
• Some incentivization

Well, it appears Yale cracked this code, of de-risked data-sharing after beta-testing it on rhBMP-2 Project based on Medtronic’s data-sharing, well enough to get J&J aboard this transparency express.

A brief read of the Data Use Agreement of the rhBMP-2 project shows what emboldened, motivated J&J with agreeing to share all its data publicly. Below is a list of clauses within the data use agreement broadly catagorized into the key aspects stated above;

Safe Harbor
Reproduced Text in “quotes”

Section 2.3 - No Direct Identifiers

“The Data will not include any direct personal identifiers ofthe study subjects to whom the information relates, nor will it identify which clinical investigators or sites contributed the data for a particular subject. Within the Data, subjects and investigators are identified by unique identification numbers, and User will not have access to the keys that relate the identification numbers to the identities of the subjects or investigators”

Section 5 - Confidentiality of Data

Across sub-sections 5.1 (obligations of Confidentiality) through to 5.4 (Survival of Obligations)

Section 6 - Subject Protection

“The Data may contain certain information that can be used by itself or in combination with other available information to identify a specific study subject (“Study Subject Personal Data”)”

This section is detailed further through sub-sections/ clauses 6.1 (no re-identification) through to 6.4 (safeguards)

Section 8 – Publications

Prevents user sharing any ‘redacted portions’ of the data fro being referred in any publication.

To the credit of Medtronic & YODA though section 6.3 (Non-Disclosure) allows user to share study subject personal data with the “regulatory authorities, upon lawful request by such authority” – It will be interesting though if a similar openness would be retained in the J&J data use agreement, given the much larger data set & hence greater regulatory implication.

Incentivization
Reproduced Text in “quotes”

Section 7 - Reporting and Use of Results

Obligates user to share all data generated from the analysis/ reserach into the sponsor data with YODA and the sponsor. Further YODA retains the right to make this report public (or not…)

Section 9 - Inventions

“In the event that User utilizes the Data to develop any inventions or discoveries, whether patentable or not (“Inventions”), User will assign to Medtronic all proprietary interests in said Inventions and in the event that User is statutorily prohibited from assigning its interest, User will grant, or ensure that the inventor grants, to Medtronic a fully paid, perpetual, worldwide, exclusive, royalty-free irrevocable transferable license for all purposes, including sub license and assignment to each such Invention without further consideration. User will cooperate with Medtronic to ensure execution and delivery of all documentation that Medtronic reasonably deems necessary to perfect Medtronic’s rights in the Inventions.”

The sheer scope of the section 9 along with the safe harbor provisions listed above makes this exercise come across more as externalization of clinical data-mining & analysis by the sponsor organization – I have no reason to believe J&J will have it any different except that the safe-harbor provisions may be more detailed, as mentioned above.

Finally, the one unstated intent of any pharma opening up its own data banks is to build pressure on the other peers and thus have insight into competitor clinical data that till date eluded them.

All said, it’s great to see transparency starting to be practiced rather than just debated about & hopefully this’ll give pharmaceutical research a chance to impact lives better than it could before.

More power to radical transparency.

Funds-on-Tap is passé & Drip-Funding is the new reality.

It’s probably been true for IT/ ITES (particularly for e-commerce and social media & app-developers) much longer, but for the drug discovery start-ups hitherto unaccustomed to expecting anything under a mio given their rather pricey research, the writing on the wall is abundantly clear - Funds-on-Tap is a pipe dream & Drip-Funding is the new reality.

Over the past year, more and more VCs have started to unveil & employ their own versions of a ‘return-maximizing, risk-mitigated investment model’ that typically involves multiplying the early-stage portfolio & bringing down the average-size of seed-investment while maintaining the overall seed-stage investment at no greater levels than earlier - A case-in-study being the recent Seed-class of Atlas Ventures & equally demonstrated by Index Ventures developing its proprietary version of MonteCarlo simulation for optimally distributing precious funds across its portfolio of biotechs' with assets across different phases of clinic.

This holds largely true for the increasingly active Pharma CVCs too that not only are mimicking the VCs in increasing their early-asset portfolio, but have taken derisking a notch higher with their joining forces* with other CVCs (competing pharma) in funding rounds, quite apparently compromising on the eventual ownership of the commercial potential &/or IP generated in the bargain.

* OPSONA (Novartis, Roche, Baxter among other VCs) AILERON (Novartis, Roche & Lilly among other VCs); MERUS (Novartis, J&J & Pfizer among other VCs)

While this may sound like life sciences venture funding is slowly turning into a mere statistical exercise (venture-farming…?), a la the stock market, knowing what it takes to separate wheat from the chaff in the complex world of drug discovery, the users of these models will surely need a lot more than a practical knowledge of the probability theory – which even a cursory read of the above posts again will make it very evident. Just may be, a biotech VC can still showcase ‘proprietary deal-flow’ as a core-strength while making a pitch to the LPs.

Now how does this lean-funding scenario impact the development strategy of the start-up? – while a few indicators of change are already out there like the CROs being encouraged (~arm-twisted) to share risk with the biotech while providing services, I believe this'll trigger bigger changes & hopefully nudge the drug-discovery towards an innovation pathway that’s a lot more rational & predictable – but then this is something Drug Baron should talk about.

So what's wrong if your drug-candidate is likely better-off as a dietary-supplement?

In a case-study, the Nov '13 issue of HBR showcases the dilemma of a R&D head grappling with the prospect of a failing clinical program & simultaneously a likely re-positioning of the candidate in question as a dietary supplement and asks its readers if the company should market it as a supplement.  The few 'responses' of some experts below the case-study expectedly range from saying aye to nay and in between.

Here's my response that I posted as a comment at the above link.

* I actually first accessed the full article through my Kindle subscription of HBR & not through the blog, hence the delay in my comment. 

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Should Caliska market L-39 as a nutraceutical?.....

A unexpectedly simplistic question at the end of a rather complex case-study by Toby E. Stuart. The question would’ve been a lot more appropriate had the case-study focused more on Caliska’s capability & track-record in development, marketing of probiotics instead of giving it a passing mention.

The question is also inappropriate since the immediate decision is not about marketing, but is about developing – Since it has been established that the launch of L-39 as a nutraceutical/ dietary supplement/ medical food is at least a year or two away (two independent, placebo controlled, randomized trials), the question should’ve been “Should Caliska develop L-39 as a nutraceutical”?

Nonetheless, here’s what I have to say against original question;

My answer is a NO & YES!

NO --> Caliska should not market the current strain of L-39 since the translocation risk can prove a greater calamity in the uncontrolled scenario of nutritional supplements.

YES --> Caliska should eventually & simultaneously market L-39 as a nutraceutical too, the why, what & how of it is as follows;

      Why?

• Few investigational drug candidates have the potential to be developed as a drug as well as a supplement & foregoing one against the other is sure a lost opportunity
• Caliska’s primary strength & track-record seems to be that of (successfully) developing and marketing nutraceuticals while also understanding the rigors of the pharmaceutical development (the very same ‘split-personality’ Hilde took an unkind and unnecessary dig at…)
• Given the super-high rates of clinical attrition in general & specifically for probiotics (quoted by the author in context of EMA never till date approving any probiotic as a therapeutic….) the odds of L-39, even as a new improved strain, of making it to the market are very low & it makes immense sense to let the consumer get some benefit of the scientific rigor that Genbac got to Caliska – If the plan-B for L-39 is a nutraceutical launch, the chances of Genbac’s science going waste are already minimized
• Finally, the fortunes L-39 would bring in as a therapeutic are limited by admission

     What?

• A new strain of L-39 that minimizes the risks associated with Bacterial Translocation (BT) – Since it’s a given that scope of translocation cannot be eliminated fully as it happens for most other native flora (within the gut) too when the subject is immunosuppressed, the developmental focus should be on the L-39's relative non-proliferative nature outside it's natural ecosystem.

     How?

• Caliska should continue the current clinical program of L-39, while in parallel registering the dietary supplement  trials with European Food safety Authority.
• The efforts of Hilde’s team at identifying the right strain will benefit both the trials above and that’s a good use of funds in these lean-times
• Caliska’s plan for both the above trials should factor-in the possibility of they having to repeat whenever the strain under evaluation is found to be inadequate & Hilde’s team comes up with a better strain
• Once some positive results are in place, Caliska should seek partners for the drug program with an intention to finance its trials (just drug not the supplement) & eventually out-license the same to the partner for marketing

Deal-Flow : Value-addition :: Silicon-rapids : Organic back-waters

Reacting to the rather weird scenario wherein some VCs are trashing their own brotherhood, Bruce Booth wonders in his latest article if this is an outcome of a Lake Wobegon-like illusion or if it is the Dunning-Kruger effect in action.

In my comment against this post, I offered my own little suggestion for this apparent case self-deprecation (OR is it not) and more....

My comment:

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If I go by what Mahendra Ramsinghani said here on LPs bothering more about deal sourcing capability than value-add by VCs, Khosla’s indictment of ‘95% zero-value add VCs’ shouldn’t really rock the boat more than the supposed shake-up caused by the AngelLists’ & Kickstarters’ of the world – The ‘80% negative-value-add’ rhetoric though is way below the belt & confounding.

Perhaps these intriguing proclamations are a manifestation of nervous energy of the PE biggies that are ‘but-of-course rattled too’ by the progressive warming of the PE globe and thus eager to reaffirm their value-add alternate asset investor status to the larger LP universe.

Can’t help but note again that a lot of the above paradigms, shake-ups, prophesies & reactions are all still relevant mostly to the 'silicon-rapids' (IT et al) and much less to the 'organic-back-waters' (~biotech) – taking a cue from what you said about the CEO, I’d think the loneliest job in the world at present probably is that of a biotech venture capitalist :-)

What when the boundaries blur between VC & PE?

My response on the highly thought provoking blog post "Venture Capital 2.0" by Drug Baron (David Grainger) - posted on 01/Mar/2013

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Once again a really thorough proposition by Drug Baron that leaves frustratingly little scope to contradict. For the sake of a debate I would still like to raise a few questions; make a few statements & generally try not to sound like mouthing a rejoinder in support of Venture Capital 1.0 - which it definitely is not! J

It is absolutely true that the VC model should periodically re-invent itself & evolve like the innovations of other kind it chases routinely – this, I believe is not just true of VCs focused on life sciences but for all others too. Also, after a quick read, I realized that one could misread the term “asset centric investing” if they do not go through what exactly Index ventures pursues through its IDDs – David, you may consider hyperlinking your statement “Asset-centric investing is only the first step on a road to improved returns for life science investors” to http://www.indexventures.com/blog/index/post/354.

Now, since the primary intent of the asset-centric-investing model appears to be de-risking venture funding to the LPs (and thus raise funds with less difficulty), the inferred premise(s) of this model appear to be as follows;

• That the early discovery prior to lead-validation should-not-be/ need-not-be venture funded

• That owing to the large investment & the inherent risk of failure, innovation (in particular drug discovery) is something better left to academic/ federal institutions & large pharmaceutical organizations that can afford the risk (did someone say, ‘risk is neither created nor destroyed, only transferred and hedged differently!’ :-))

• And finally that any VC backed biotech with a “pipe-line” hasn’t probably thoroughly screened the clinical & commercial viability of candidates including, probably in a few cases other than, the lead-program candidate for which it managed to tease out some funding?

No doubt this model makes absolute sense to the fund of funds or LPs on its focus on sheer reduction of risk to IRRs but not sure if this model helps generate & nurture novel enterprises & why should it? - now I do realize that the ACI model also believes that creation of an innovative enterprise is NOT the VCs responsibility (probably since they are using ‘others money’ for this noble cause? J) & more a responsibility of the struggling entrepreneurs themselves?

Without sounding too knowledgeable about it, I would like to believe that across the past few years, VC seemed to have played a role in keeping afloat the spirit of enterprise at the most critical & vulnerable early stages and thus helped, however minimally, in letting a lot of budding innovators take root & grow their enterprises into cash-cow organizations that’d offer a lot more de-risked alternative asset investment options to the LPs.

So while I generally & unequivocally support the need for yet another paradigm shift in drug discovery methodology & innovation models, I am not sure if a VC model de-risked to this extent almost morphing into a PE would help this innovation paradigm nor help create the much needed pipeline of early innovative enterprises that later mature into investable asset-centric organizations.

Post thought:

In the current context of drastically reduced spend on basic discovery by big-pharma, I see that most most biotechs, drug discovery organizations have started to reinvent themselves into “drug development organizations” and have quite voluntarily started de-risking by building a pipeline/ portfolio of in-licensed/ spun-off ~pre-validated drug candidates . So I guess without so much as a nudge, the enterprise out there is all ready for Venture Capital 2.0 – Now again that doesn’t say much about the survival chances of real innovation that not necessarily stems from the largest of organizations/ institutions….. after all, garage innovation in life sciences appears to be a distinct possibility in in these winds of open source drug discovery.

Dialog on Drug Baron's post "The Primacy of Statistics: In defense of the pivotal Phase 3 Clinical Trial"

The Primacy of Statistics: In defense of the pivotal Phase 3 Clinical Trial

By Drug Baron (David Grainger)

http://www.tcpinnovations.com/drugbaron/?p=319&utm_source=rss&utm_medium=rss&utm_campaign=the-primacy-of-statistics-in-defense-of-the-pivotal-phase-3-clinical-trial

My comment on the above post;

A very compelling argument indeed - One factor though I think needs to be taken into account is the type of indication for which the drug is being pursued.

While for the more prevalent indications such as metabolic disorders, cardio-vascular diseases et al where the sample size is large statistical rigor is highly relevant & decisive while approving the drug, can it be simultaneously argued that for orphan & other highly specific indications, where the sample is small, a solely statistical model will eliminate a lot of potential treatment options to statistical bias? – particularly since its being increasingly noted that an individual’s genetic make-up (presence or absence of mutations on a specific gene et al in the healthy or diseased tissue) can determine how the patient responds to the drug under evaluation? (case-in-study, Vemurafenib working for BRAFV600-Mutation Positive Metastatic Melanoma patients)  

Drug Baron's reply t my above comment:

davidgrainger Mod  Murali Apparaju • an hour ago

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Thanks for your comment. This goes right to the nub of the argument.

You are exactly right that the slavish adherence to statistics will deny people (particularly in small indications) access to medicines that do actually work. In the limit, unless you are an identical twin, you are the only person with your genotype and maybe the drug would work brilliantly for you and for no-one else. With statistics as the gatekeeper, you will never get access to that drug.

BUT the key point of the piece is to point out that without statistics there is no way to know if that drug really did work for you. There is no control. At present (and maybe always) there is no alternative to a statistical test to be sure that a drug works at all.

Unless you are happy to approve drugs that MIGHT work, then we have no choice but to accept that with a statistically significant phase 3 trial as the "gatekeeper" we will reject drugs that actually work, but which we cannot prove they work.

For me, I would rather have the current system - where drugs have to be proven to work - than the one that existed prior to regulators, when snake-oil salesmen could sell anything as long as they could assemble a compelling enough argument to persuade the purchaser. That was a bad model - but allowing drugs through that havent passed a statistical test simply because they may work in some people, and there arent enough people to do the proper test, is a big step backwards.

Yet I see that happening more and more, particularly in the orphan drugs space that you plead as a "special case" - which is precisely why I wrote this article!

Has the rise of an Indian sun in drug discovery horizon turned out a no-show? OR is it a mere eclipse?

Looking up on google to put together my next post, I typed out the text “Drug discovery prospects India” and the top most hit was that of a 2012 Current Science study that went on to explain how the authors figured that the prospects are poor for original drug discovery in India. Not quite the encouraging start I was hoping for.., I scrolled further down and I find the counter poser, a report by Kauffman, no less, that predicted a bright future for drug discovery in India way back in 2008.

While the 2012 article, incidentally by Indian authors, isn’t necessarily a very brightly designed study and the Kauffman analysis isn’t exactly reeking of academic rigor, together these reports do raise the pertinent question of, if the rise of the Indian sun in drug discovery horizon turned out a no show? or is it a mere eclipse?

To part validate the above hypothesis, I went about tracking the flow of funds into life science enterprises within India in the past four years – some observations;

• Considering the 2012 article slams the quality of innovation of Indian CROs,  the discovery services companies ironically cornered >40% of all the investment made in past three years
• The investments into medical devices & diagnostics pretty much followed the global trend which has been incremental over years  
• Manufacturing organizations, both biotech & small molecule attracted some investment, I’d guess a sentiment again aided by a hope of continued & incremental global outsourcing
• Drug discovery organizations receiving venture capital rank at the very bottom of the list at 8% (as against 30% globally)

Even a cursory scan of the existing drug discovery strategies within Indian firms throws up the following aspects;

• A lot of ‘me too’ approaches/ platforms, including choice of target protein that may have already lost out the race to the plethora of US/EU innovator organizations
• Continuing the above line, a lack of novelty of approach, something that’d make an investor sit-up and take notice
• Incomplete, inadequate composition of scientific-leadership teams  i.e. key functional leaders & a sound advisory board
• A surprising lack of in-licensed drug candidates in the portfolios vis-à-vis’ efforts on building novel molecules from scratch
• A similar lack of high pedigree academic partnerships, Indian as well as overseas
• Last but not the least, a surprising lack of any focused attempt to use make use of the India-specific advantages like drug discovery based on Traditional & complementary medicine et al

As with most SWOTs, all the above weaknesses can be worked on and converted into opportunities. Looking at the diaspora of top-notch Indian chemists, molecular biologists, bio-physicists, pharmacologists across the globe making highly innovative & astute contributions to the drug discovery, development & clinical evaluation, I’d readily dismiss any talk of Indians not being up to it when it comes to path breaking innovation – only there is a definite need to re-purpose Indian drug discovery enterprise model, if I may say so & probably this is true for most other domains even.

      

Now, who’ll bell the cat? I say why not the investing universe?  of all geographies and domains out there, Indian drug discovery enterprise is where there's a crying, albeit unacknowledged, need for some astute thought leadership and strategic oversight so as to build, nurture & steer the foggy but promising entrepreneur pool - and who better than the venture capitalist to assume this constructive role, shift the paradigm & eventually partake the fruit of success?

Food for thought.

AFTER THOUGHT:

It’s about time the IRR of an Indian discovery organization is determined by the sheer value of the IP & portfolio it generates and NOT on whether the company is incorporated in Boston, Basel or Singapore.

Pfizer Venture Investments (PVI) - a quick analysis of portfolio companies, categories

Trying to understand the driving factors behind the trends of life science investments in 2012, I was wondering if VC & CVCs behave differently or if one determines the trend & other follows it largely - which I realize is putting it too simplistically and perhaps the VC operates as one organism.

However, I believe that, with the genericization troubles looming large, the big pharma started to rationalize the product development strategies by taking into account parameters which hitherto were not given a serious thought.... foremost of which I'd guess is consumer behavior - This new diligence I expect will translate into the way big pharma CVCs have been building their portfolios over past 3+ years. 

Based on this premise, I tried to analyse the PVI portfolio & see if the data throws-up any tangible trend. Since I was unable to find the exact value of the funding in most cases (the funding rounds involved more than one VC, hence), I stayed with number of investments & hopefully the trend will still make some sense; 

A snap-shot of investment across innovation categories:

Some trends:

• Medical Diagnostic investments equal Drug Discovery numbers (& not in all cases it is merely companion diagnostics related investment)
• Enthusiasm for Medical devices & equipment is much lower than the overall average in 2012 (~50%) - However this I feel is still significant, as logic says a medcines company would be more interested drugs than devices
• Interesting appearance of investments into companies that'd contribute to research /business/ operational advantages for the investing big pharma - surely pro-logical, but interesting nonetheless & showcases the emerging realities in sustaining business
• Drug discovery at 30% only marginally higher than the 23% overall in 2012

Within the drug discovery investment, the innovation sub-categories point to a definite preference to go after platform technologies that'd generate leads in multiple therapeutic domains/ indications;

Overall, very interesting & I will hopefully continue this line of thought with another post or two.

Comments?

Drug discovery unable to attract big money! - Is innovation, rather the lack of it to blame?

Some interesting observations on early-stage funding for healthcare from the 2012 Venture Capital Activity Report published by CB Insights (report abstract at this link);

• Healthcare gets a not-so-insignificant share of 23% of all venture capital in 2012, but the overall investment into healthcare is lower than 2011 numbers, inline with the overall decrease in VC funding from previous year

• The year also saw overall deal-sizes within healthcare fall from 2011 levels,  again like in other industry segments

• Within healthcare, medical device & equipment related investments took 40% of the total dollars distributed and this shift of money towards devices & equipment segment has gotten stronger in 2012

• Within the remaining 60%, drug discovery, development & biotechnology seemed to have got ~35% share, of which chemistry based drug discovery/ development got ~20%
• and finally, within the 35% share share towards drug development, a majority seemed to have gone towards late-phase funding (>60 %?)

Thus the funding received in 2012 by individual companies towards early stage (discovery pre-clinical et al) seems much lower than the 2011 average (while ~10mio USD seems to be the average deal-value for all phases included, ~2 million USD could be the average value for early phase funding) - I don’t see any reason to believe that 2013 will be any different and if this trend indeed continues, the introduction of new candidates into clinic will continue to lag as before and economizing the cost of discovery & early-development will continue to be a rational strategy to be employed by the small & virtual discoveries - not sure if that'd compromise on innovation further....

The tilt of VCs towards medical device/ equipment segment looks like a commonly employed de-risking strategy of most investors. It also simultaneously suggests a seemingly prevailing weak-sentiment in investor universe towards the quality of innovation happening in biotech & chemical drug development.

While innovation domain should go through its own disruptive innovation now...., any major positive swing from 2012 trend would happen only if GPs (& LPs of course....) innovate their conventional low-risk investment strategies resulting in a) significant increase in number of deals and b) an appropriately incremental average funding on each deal and both towards drug development. 

So when is the new paradigm shift in drug discovery happening & who is going to drive it?

The clinical attrition of INX-189 post a 2.5 billion acquisition - are investors into life sciences really looking at where the buck is headed?

October 2012
Discussion initiated onGlobal Private Equity & Venture Capital group on Linkedin

http://www.linkedin.com/groupItem?view=&gid=48513&type=member&item=156370875&qid=b8ecfd7b-c40b-491c-9e3d-f3f42e0780e4&trk=group_search_item_list-0-b-ttl&goback=%2Egmr_48513

Agreed BMS is no VC & acquisition of Inhibitex at 2.5 billion was more a survival tactic, but probably the outcome could be such for many investments into the life science (drug discovery). I believe the investor due-diligence of the investee should go beyond market projections of the pipeline candidates & a rational assessment of the druggability & clinical longevity of the pipeline candidates is what should interest the investor the most – not sure if this happens to the extent required?

Would love to hear what the investor community feels about this.

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PS: My love went totally unrequitted :-)... zero response

INX-189 clinical attrition - a call for re-look at single isomer strategy of Gilead?

October 2012

Discussion posted Pharmaceutical Discussion Group on LinkedIn

http://www.linkedin.com/groups/INX-189-clinical-attrition-call-38263.S.156348010?goback=%2Egde_38263_member_103345417

Is the purported toxicity of the non-active diastereoisomer in a P-chiral nucleotide prodrug (protide) a scientifically derived hypothesis OR is it merely a surmise from a coincidence that no active-isomer is found toxic till date? (considering very few 'single isomers' entered PI till date..)