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

• −

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.

USER TRUST, the dope that can't be ignored in the race to monetizing cyber-social engagement – A commentary in light of the recent revamps to LinkedIn user experience

Okay, here goes…

FEW STATS & STATEMENTS..

With a market cap of over US$16 billion & revenues forecast slated at US$1.4 billion and supposedly* out-pacing the original social media biggie Facebook in terms of revenue v/s user base, LinkedIn is surely fanning the flames of market expectation of an aggressive performance coming year (*the revenue per user as of last financial year is ~ US$5, coincidentally for both LinkedIn & FB)

As a part of this expectation frenzy, the analysts have been postulating various acquisition targets based on LinkedIn’s need to grow faster, hence inorganically through acquisitions, though not all necessarily as pricey as Slideshare buyout and generate more revenues & earnings that’d justify its two years into public listing - In a funny kind of way, I feel the financial markets almost want LI to compensate for the laggard performance of Facebook J

SOME RANT & RIFFS..

As a regular user, I’ve been wearily noticing the rapid dilution of what used to be the core value-add of LinkedIn platform (vis-à-vis’ other social media) – its high quality user-experience!

While a major portion of this dilution happened through the unceremonious withdrawal of various tools & applications, a lot of it is also owing to the subtle or probably not-so subtle attempt to move away from being an egalitarian professional platform to becoming an elite platform where a few celebrities & myriads of followers exist at different levels of social relevance effected through a methodically tempered and manipulated 'visibility engineering' by the overseers……. not sure about what I’m saying?... ponder this;

Unceremonious WITHDRAWAL of apps

• Just like that, one fine day most used & adored apps such as MY TRAVEL (TRIPIT); EVENTS; READING LIST BY AMAZON (along with all my reviews), BLOG LINK et al are all gone!! - Ironically, the settings still point me to the applications page where all the above application icons still exist, but defunct.

The subtle social DISENGAGEMENT:

• STATUS UPDATE - No more one can use Twitter to update the LI status, the other way is possible though. Also, the status update is now “just one more activity” on your profile & the moment you post a comment on anything else, your status update goes into hiding below. Furthermore, your comment on a LI article itself is never shown, but a grab of the article on which you commented is displayed on your profile
• ENGAGEMENT - The LinkedIn Answers is gone…. taking with it the zillions of high quality & ‘free’ opinion and advice

And what features get strengthened? 1) JOBS - with the introduction of talent solutions; Premium job-seeker et al 2) NEWS - with LinkedIn Today, Signal et al 3) TALENT SOLUTIONS – introduction of Skills and Expertise endorsements moving away from the much cumbersome recommendation 4) COMPANIES – with enhanced options for engagement with potential business associates and job aspirants et al and finally 5) PREMIUM USER ACCOUNT and the paying account privileges that come with it.

PUTTING STATS & RANTS TOGETHER..

Reading the trend of vanishing apps & features together with the names of potential acquisitions floating about, it does appear LI could end up acquiring and integrating a few companies such as;

• VIADEO & ChinaHR  - to ramp up the user-base and thus the revenues
• QUORA – to compensate for Answers & recreate the lost cause of stimulating user engagement.. and finally,
• DEMANDBASE – to optimize the momentum of COMPANY pages and create a B2B integrated transaction platform

I don’t believe acquisition of MONSTER is something LinkedIn would/ should bother about?, as LI already enjoys the benefit of a better user perception (real?) of candidate quality plus a greater brand equity, which any association with a hard-core job site like Monster would only dilute.

Essentially, when the analysts out there propose these acquisitions, it’s all about money, valuation, market capitalization & essentially monetizing all the user-base unabashedly quite like what FB is trying to do.

THE MOMENT OF TRUTH..

But of course, these are enterprises after all and they’d want to make money & people who invested in those want them to make money. But when the very basis of a business is its user base, their interest and trust in the platform and it’s ethos, I am not sure if the solely revenue-inspired changes LI is affecting make complete sense.

I want to believe when LI web-page redirect I landed on says “We'll be focusing our efforts on the development of new and more engaging ways to share and discuss professional topics across LinkedIn” – I very badly want to……. I love/ loved being on LinkedIn, I want it to sustain my interest, I do want to still confide all my professional details to the platform without having a niggling doubt that LI is only teasing-out information it could use commercially and blocking-out information it can’t monetize – only I don’t see many signs of it. I, an average but avid social media denizen am not surely alone in this feeling of the user getting left high and dry in this chase of valuation.

I hope LinkedIn is listening & FB eavesdropping..... Please don’t do the mistake of taking the user for granted 'cause on a social media user is the primal stakeholder.

Cheers!

AFTER THOUGHT..

Is LinkedIn itself a candidate for take-over? I’d think so - it’d be the right acquisition for any company out there trying to dominate the cloud scene with an integrated gadget to boot. Would one of you gentleman please raise your hand? Tim, Jeff, Larry… anyone….??

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?

Awards: So what if there are some & some win them?

My comment today on the latest blog entry by A VC @ http://www.avc.com/a_vc/2013/02/award-shows.html

When I'm in a business and I’m courting investors & clients alike all the time, out there if there's one event that has a better brand equity than my new start-up's wet-behind-the-ears name has...., I'd surely want to jump right in & improve my chances of getting that extra nano-sec of attention, exposure and the possible business that could come along - please note my usage of would, could - no guarantees here folks, like in any investment, there's only hope which is not always merely fond...

Surely, self-nomination requires some amount of self-assuredness if not cocksureness...& if the few eyeballs I got when I figured in the nominations turn to lot more when I win - hey, am not complaining - you shouldn't even!

IRR v/s Social Impact: Do financial institutions necessarily go through this dilemma?

The news on Times of India Social Impact Awards & what Nicolas Aguzin, chairman and CEO of JP Morgan- Asia-Pacific said during his speech there about JPM's commitment to its social responsibility triggered a cackle of thoughts that're simultaneously standalone, contradictory, inter-connected and inter-dependent;

• CSR (Corporate Social REPONSIBILITY) isn’t necessarily the same as CSI (Corporate Social IMPACT)
• Given all the progress out there in the science of measuring impact, it’s possible a lot of companies have figured out OR will figure out sooner than later, how they could reposition their CSR as CSI
• In an effort to make their social impact measurable, it’s possible that corporates' inadvertently project & expect social-change in a defined, time-bound (& not practicable) fashion?   - While objectivity & accountability are a must, through my wife’s  work in the development sector (at an implementation level..), I could sense/ witness how some inappropriately designed impact measures of a funding organization can/ have killed or maimed a promising social initiative, which if supported on a longer term could've indeed resulted in replicable, scalable & sustainable social change
• Finally, if not blatantly so, at the very root most CSR initiatives tend to carefully (& smartly?) avoid any conflict of interest with the organization’s business goals – while this is understandable since the very purpose of a business is NOT social impact but profitability in the longer-term, it definitely makes more long-term business sense to ‘tangibly’ align the CSR/ CSI with an organization’s core business mission. While I wouldn’t risk associating this with the “social business model” of Prof. Muhammad Yunus, I’d think it’s nevertheless related, but limited to formulating the CSR plan – Social-Aligned Business Responsibility-SaBRe anyone?? :-) 

While attempting to apply, superimpose the above ethos onto the social sensitivity of the investing universe out there, I could only come up with a posse of questions, but no obvious answers – ponder this;

• What would amount to a social impact of a financial institution (LP)? – i.e. apart from making sure the eventual investments (through GPs) are in alignment with certain mandated geo-political guidelines – I do see some institutions following macro-level charters like the Equator principle et al & that’s no doubt a great start, but not sure if that’s comprehensive enough in all complex geological, social contexts and effective for what length of a long-term?
• In a climate where the accepted investment efficiency measures employed are the time-bound investment-to-exit cycles & IRR, is there a safety catch, any checks & measures that’d  ensure sustenance of an innovative enterprise that may have a greater social impact, if not an eye-popping ROI?

Food for thought…

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?

Generic Drug User Fee Act (GDUFA) - What will be the implications for the consumer & for the generic API manufacturers based outside NA & EU

20 August, 2011

Posted in Linkedin Answers by Murali Apparaju

For those who remember SOCMA & EFCG making a fervent pitch in 2006 for a level playing field for domestic (read: NA/ EU) and foreign (read India, China) API manufacturers, this is an announcement of their first success & how.....

Two days ago, GPhA, EFCG & SOCMA reached an agreement with US FDA on the proposed final form of the Generic Drug User Fee Act (GDUFA).

While at the conceptual level this act is for higher patient safety through a tighter regulation of Ingredient manufacturer, this also appears to be an apparent back-door strategy to wall-out "old-technology" (read: "No QbD/ PAT" also read: "Cheap") Indian & Chinese API manufacturers in favor of the more-regulated, domestic, safe & costlier? local manufacturers.

(the NY times brief in the above link is titled "A deal to get Cheaper & Safer drugs" - wonder how exactly was this deduced?!)

What do you think GDUFA will eventually achieve/ cause & do you think consumer is the real beneficiary?

Hoping to see some comments here.

Cheers,

Murali Apparaju

NRAchists in gun-afflicted america....

December 2012

My comment on a LinkedIn article on need for Gun Control in USA, I only see the comments now, no article!!, still an interesting read...

http://www.linkedin.com/today/social/comments?articleId=5686805067156422750&offset=15&limit=365&trk=tod2-all-comments

As per the chart, USA has ~90 guns for every 100 people. Despite this startling fact, I still see many below demanding a more scientific & non-discriminatory analysis rather than brooding over the above fact. - know what, to hell with more stats.... it is probability! - the probability of a gun being used is directly proportional to the number of guns that are available for use........ stop kidding yourselves gents & ladies, face it instead & save the kids.

Caste, gender & slur - Quite an explosive cocktail!! :-)

01 March 2009

Wow, this repro' is a dinosaur, way back from 2009!!! - my comment below was on a real flamer of a topic that was originally posted in November 2007 & still going strong with 983 comments amounting to terabytes of sane words & insane rhetoric. I don't want to be another blogger to do the same mistake & hence have disabled comments on this - If you have a compulsive impulse to add to Uday's woes, post your comments on the original site below - cheers, V 

http://udayms.wordpress.com/2007/11/16/brahmin-guys-are-not-lovemarriage-material-says-brahmin-girl/

My observations on the original post (rather on the content of Brahmin Ponnu’s statements) – to keep it simple, I will assume she’s indeed a brahmin ponnu & the feelings indeed are true…

I)

“Familiarity breeds contempt – Over exposure to a certain kind makes one nauseated – the insider knowledge causing prejudice”

•  Doesn’t this happen in your company, aren’t the insiders the last choice for the new post created & don’t outsiders look eminently more attractive than insiders to the management – this is a similar syndrome.

II)

“Choice of mate instincts keeps changing with age..”

•  At college I’m sure the lure is of big talking, macho & adventurous guys – which an average brahmin male may not demonstrate owing to upbringing.. PHYSICAL & SOCIAL QUALITIES COUNT WHEN ONE IS LOOKING FOR A PRINCE ON THE WHITE HORSE TO TAKE YOU ON A DATE – SWEEP YOU AWAY?….FOREVER?….. THINK AGAIN…
• 5 years down the line, I’m sure ponnu would settle for a Bay area techie in favour of the college stud who may not have settled as well & earning that well – MONEY COUNTS WHEN YOU ARE LOOKING TO MARRY

III)

“The lady’s comments are possibly reflecting the general liberation of minds in either sexes in this modern age…”

•  Perhaps an indication of a growing & general reluctance to accept limitations in partners & aversion to compromise.
• May be polygamy/ multiple partners is making a come-back… (check out the Axe Deo ad where mixing makes babes better….:-))
• Perhaps, the ever increasing domination of “I” over anything else

IV)

“Brahmin men caught in a time-warp? – starting to live the stereotypes showcased by society, films??

• Someone said this before, buck-up guys, change, work-out, change your attitude to looks, you have the basics in place, all you need to do is polish the stuff..
• Forget about the simplicity your grandfather so believed in — he was in a different era… re-package your body, spirit, get attractive to the opposite sex…
• I’m sure those who have done/ doing this already see the results, non-brahmin girls falling for them & yearning for them… (all the above applies still to these wide-eyed wonders, grass is greener on the other side of the fence)
• finally it’s an appraisal, part-true, part-crap —- well…take some good out of it…. emerge better… don’t justify & get labelled more harshly…

all the best…

3200% premium for innovation!!

April 2012

Discussion posted on Pharmaceutical Discussion Group on Linkedin

http://www.linkedin.com/groups/PhRMA-says-price-as-trigger-38263.S.105200659?qid=8b279aac-88f8-4538-b788-061d5b62bd1d&trk=group_search_item_list-0-b-cmr&goback=%2Egmr_38263

PhRMA says price as trigger for compulsory license is not provided for in TRIPS - wonder if TRIPS provides for 3200% premium for innovation?

Reference article:

PhRMA’s Special 301 Comments on Indian Compulsory Licensing...infojustice.org

PhRMA’s Special 301 comments to the U.S. Trade Representative include a section on the compulsory licensing provisions in India’s Patents Act.  PhRMA recommends that “India should ensure that the CL provisions comply with TRIPS...

Why won't Gates spend a few more cents (per dose) on non-mercury biocides & shut-up the vaccine detractors?

April 2012

Discussion posted on Pharmaceutical Discussion Group on LI - by Murali Apparaju

http://www.linkedin.com/groups/Why-wont-Gates-spend-few-38263.S.109547291?qid=8b279aac-88f8-4538-b788-061d5b62bd1d&trk=group_search_item_list-0-b-cmr&goback=%2Egmr_38263

I remember trying to promote ProClin (Supelco) as a viable safe non-mercury alternative to Thimerosal (Sigma), both Sigma-Aldrich products for the uninitiated - I've seen that despite obvious interest & some intention, vaccine manufacturers solely surviving from the bulk purchases by the likes of gates foundation continued to use Thimerosal owing to the cost-advantage it offers in a climate of 50% price fall each year… - 7 years hence, I’m wondering if all the noise on autism by Trump motivated Mr. Gates to at least encourage his supplier base to start looking at safer alternatives to Thimerosal albeit at a few cents higher per dose?... if not, why bill?

Reference video 

Why Bill Gates Is A Hero And Donald Trump Is A Zero - Forbes forbes.com

Donald Trump should stop creating fear about vaccines, which are safe.

Review of Mahendra Ramsinghani's "The Business of Venture Capital: Insights from Leading Practitioners on the Art of Raising a Fund, Deal Structuring, Value Creation, and Exit Strategies

21 Aug 2012

Review Posted on Amazon.com
http://www.amazon.com/review/R2Q6WI836ZOCJT/ref=cm_cr_pr_perm?ie=UTF8&ASIN=0470874449&linkCode=&nodeID=&tag=

A 'must' for all those who fancy the bucket & probably the ocean too!, August 21, 2012 By Vishrasayan As someone aiming to venture into VC, and moving quite laterally at that, I was on lookout for a book that not only strengthens my basics but would also help me develop my own perspective of how the ecosystem behaves & how I could synergize and coexist with the same - `The Business of Venture Capital..' by Mahendra Ramsinghani fit the bill perfectly. While essentially structured as a comprehensive guide to the VC process, the author took pains not to make the style pedagogic & peppered it liberally with quotes, case-studies and his own witty one-liners that helped the overall learning process while not getting your goat. Even as I persisted through all chapters, I did realize that the composition of each chapter allows one to skip a chapter or two & still make sense of the flow. The book ends with a quote by David Ogilvy "Don't bunt. Aim out of the ballpark. Aim for the company of immortals". Interestingly (for me at least...), the epilogue starts with the sentence, "At its core, VC is truly an apprenticeship business" - This seeming contradiction/ irony is what defines the approach taken by the author Mahendra Ramsinghani in establishing that a true venture professional is essentially a lifelong apprentice who nonetheless perpetually aims to challenge the boundaries of a conventional success. Highly recommended for aspiring & established VCs and anyone else who fancies the `bucket' in whichever way!

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.

----------------------------------

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

Is the LP bias against investment into life-sciences contra-logical?

17 January 2013

Early Stage Biotech Showing Positive Signs of Scaling Its Wall of Worry by Bruce Booth on Forbes

http://www.forbes.com/sites/brucebooth/2013/01/15/early-stage-biotech-showing-positive-signs-of-scaling-its-wall-of-worry/ goback=%2Egmr_38263%2Eamf_38263_16107339%2Egde_38263_member_205146678

Despite the apparent consensus opinion at JPM that innovative new start-ups are continuing to attract capital, I wonder if in reality the venture funding, particularly from big-pharma CVCs, is mostly channeled into development/ acquisition of potential clinical candidates - THIS anomaly of an 'uncharacteristic aversion of domain biggies themselves towards investing into early innovation that'd feed their own pipelines' is WHAT I feel is the primary reason for a strong bias in the LP universe against investment into Life Sciences......

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..)

The quintessential 'Indian vegetarian meal' prototype on Emirates

23 Nov 2012

On FB McKinsey article "the trouble with Travel distribution" 

http://www.facebook.com/mckinseyquarterly/posts/432757166778183

Yes indeed - the globe trotting traveler these days can negotiate and get deals on anything & everything, except if he/she's an Indian vegetarian, flying any global airlines and hoping for a gourmet food experience.... Get real chum, eat ur paneer, okhra, rice & all together :-l

Akbarnama

11th January on FB

Akbar bhai.... meraa bhi ek sawal hain aapko......jo baataan shadab cafe mein chai pe chotti samosa khatey waqat bolney hain, woh baataan camere ke samne kaiku karrain miyaan? panga kaiku lerain phursat mein khali-peeli sarkar sey? 

The mahaul at Nirmal is such that anyone can get into a rhetoric mode, get irrationally impassioned and indulge in senseless bravado....... while some of the allegations, sentiments voiced by Akbar bear a semblence to reality, truth, a lot of it was hyperbole & it would be foolhardy to say the listener would take it all as God's word...... Akbar is no polished politico, he comes across as immature, kiddish...... more than what he said about the infamous 'pandrah minute', more worrying is the way the crowd erupted in cheer & approval of that idiotic posturing........... dimaag khaan bhoolkey phirrain yaaron ye logaan?

Secular India would do good to focus on the funny side of all this & show it to the understanding Muslim population out there which also has a sense of humor... (believe me... there were a few concerned, confused and amused faces right behind the sher-e-deccan :-)...) to me this speech is nothing more than a excitable shahri showing off to the vulnerable dehathi....

(main section is between 48th & 60th minute)

Climb down from the towers BoDs..

We are all Board Members on LI by Lucy P Marcus

http://www.linkedin.com/today/post/article/20121120235138-60894986-we-are-all-board-members?trk=mp-reader-card

As an employee who always worked with a sense of ownership, accountability, I always felt its strange that the board's engagement with key employees (second line, executing level) within the organization is non-existent & more often than not, its strategic guidance is based on a colorful slide-deck or an birds-eye-view executive summary that rarely reflects the subtler aspects of business realities and it's short & long-term sustenance. While I see a common thread here that the board has a responsibility towards company's vision & and should represent the stakeholders interest rather than it’s own, I am wondering why so many critical decisions are still taken by boards without ever engaging directly with the stakeholders that actually go about translating the vision into action? & I’m presuming that employees at key positions too are considered a part of the stakeholder pool & not just the investing PE universe.

Provoke, par zara bachkey :-)

Want to Deepen Impact in 2013? Be a Provocateur on LI by Ben Mangan

http://www.linkedin.com/today/post/article/20130104051308-132220-want-to-deepen-impact-in-2013-be-a-provocateur

Quite nicely provoked :-)... I though see most provocateurs use the 'why' primarily for disruptive purposes (unfortunately) than otherwise.... I guess these belong to the category of 'those who don't give a damn (like Veronika J wrote below...), but provoke nonetheless for the heck of it' (OR to topple some apple-carts...) Whichever type one is, my message to all prospective provocateurs is "Ask WHY?, but be well prepared when countered by 'WHY NOT'?" 

Your message bothers me Esther and how....

Should I Bother With Your Message? Persuade Me! on LI by Esther Dyson 

http://www.linkedin.com/today/post/article/20130116205459-28157-should-i-bother-to-read-your-message-persuade-me?goback=%2Eptf_*1_*1_*1_*1_recentPosts_*1&trk=who_to_follow-b

With all respect to the departed soul, I'm starting to get why Aaron Schwartz decided to end his life...... sender of a message pays on a social network? - Monetizing a few lines as though it were a validated piece of patented intellectual property? – bad enough reason for any cyber-socialist to give-up on hope and die! 

I remember & believe that cyber communities/ DBs started out in a spirit of sharing knowledge, thinking & perspective with whoever displays a similar trait to engage & evolve. If companies like LI & FB monetize this engagement for their own stock valuations, I still understand, particularly seeing how FB is struggling with its sub-par listing & trading post such a hyped-up public issue. What I don't understand is the increasing tribe of self-appointed thought-leaders & experts who believe a mere mail to them deserves a valuation!!!!! – Is it that I should’ve been a citizen of Pandora OR Is this really the most obscene manifestation of assumed self-importance? 

If I have a need that requires me to pay to someone just so that he/she receives my mail in a non-spam folder & for which he/she may not necessarily respond even, I’d think my need itself is ill-articulated &/or illegitimate and the person whom I’m trying to pay to get through to isn’t worth reaching out to after all 

Indeed, a good self-image is important in life..., but gents & ladies extreme self-importance is avoidable - never forget the “Rule Number 6” (http://dannyhageman.wordpress.com/2011/06/21/never-forget-rule-number-six/) 

Cheers