Friday, May 27, 2016

UPDATED: Additional Securities Of OpGen Due To Be Acquired By Merck Affiliate: Now 37.5% Holder


This post updates mine of Tuesday. In that post, I suggested that Merck would use this tech to lever its way into a continuance of the front running position Cubicin® holds, in hospitals (despite a generic threat starting at the end of June 2016). I still think all of that holds, but in view of the next paragraph, I think this investment is becoming an ever more important vehicle for Merck. Why? Well. . .

With news breaking yesterday that the US has seen its first completely antibiotic resistant (mutated) E. coli bacterial infection in a hospital in Pennsylvania, the urgency to find at least one additional line of last resort treatment -- in anti-bacterials just. . . flared orange. As of yesterday, we don't have one, apparently. Due to a naturally-occurring but evolutionary plasmid splice, it seems, the Pennsylvania case presented with colistin-resistant E. coli. Colistin was the last agent known to work when nothing else would.

And so, the pharma community is accelerating its efforts (and investments) aimed at finding something "beyond" colistin -- in order to stay one step ahead in the antibacterial mutated/evolutionary "arms race". From the just filed SEC Schedule 13D Amendment, then:

. . . .On May 18, 2016, the Issuer entered into an amended and restated securities purchase agreement (the “A&R Purchase Agreement”) with certain investors named therein, including the Purchaser which amended and restated the securities purchase agreement dated as of May 12, 2016 (the “Original Purchase Agreement”).

The A&R Purchase Agreement amended the Original Purchase Agreement to provide for the purchase, at the election of each Investor, of units (“Units”) consisting of (i) either (A) one share of the Issuer’s common stock, par value $0.01 per share (the “Common Stock”), or (B) one share of non-voting, convertible preferred stock par value $0.01 per share (the “Series A Convertible Preferred Stock”) and (ii) warrants to acquire 0.75 of one share of Common Stock (the “Warrants”).

Under the A&R Purchase Agreement, the Purchaser (i) acquired from the Issuer 1,200,000 shares of common stock and warrants to acquire 900,000 shares of common stock on May 19, 2016 and (ii) will acquire from the Issuer 2,734,427 shares of common stock and warrants to acquire 2,050,821 shares of common stock at a second closing under the A&R Purchase Agreement to occur within 60 days of May 19, 2016.

Pursuant to the A&R Purchase Agreement, the Issuer has agreed to provide certain mandatory registration rights and piggyback registration rights to the Investors in respect of the Shares and the Warrant Shares customary for this type of private placement. Specifically, the Company has agreed to file a registration statement on Form S-3 (or other registration statement, if the Issuer is not then eligible to use Form S-3) (the “Registration Statement”) within 60 days of execution of the A&R Purchase Agreement. The Issuer has agreed to keep the Registration Statement effective until all Shares have been sold by Investors or may be sold without restriction under Rule 144, promulgated under the Securities Act of 1933, as amended. In addition, to the extent that the Registration Statement is not available, the Investors will have piggyback registration rights with respect to a registration statement that the Issuer proposes to file (subject to certain exceptions). The Issuer will pay all fees and expenses incident to the registration rights provided to Investors.

In addition the A&R Purchase Agreement provides that, for a period of two years, Investors also have the right to participate on a pro rata basis in subsequent offerings of the Issuer (subject to certain exceptions). The A&R Purchase Agreement also provides that, for a period of 90 days from the date of the Securities Purchase Agreement, the Issuer is prohibited from issuing any Common Stock or securities convertible into common stock (subject to certain exceptions). In addition, the Issuer’s officers, directors and holders in excess of 5% of the Issuer’s outstanding Common Stock have agreed to enter into a lock-up agreement in connection with the Offering, which generally prohibits them from selling securities of the Issuer for a period of 90 days from the date of the A&R Purchase Agreement.

Common Stock Warrants

The Warrants will be exercisable at an exercise price of $1.3125 per share of common stock, will become exercisable 90 days after the date of issuance, and may be exercised for five years. The exercise price and the number of Warrant Shares will be adjusted to account for the subdivision or combination by the Issuer of outstanding shares of Common Stock. The exercise price may at anytime also be voluntarily reduced at the discretion of the Board of Directors of the Issuer. The Warrants may be exercised pursuant to a cashless exercise, but only if a registration statement covering the resale of the Warrant Shares that are the subject of an exercise notice is not available for the resale of such Warrant Shares. . . .


Well -- now you know. And my theory remains that this is a dove-tail deal, for the former Cubist franchises. Grinning ear to ear, here. . . g'evening. . . .

Legacy Schering-Plough Comp. Committee Chair Once Again (5 Years Running!) Received Fewest "Yes" Votes -- Saw Highest "No" Votes -- At Merck's Annual Shareholders' Meeting


On this sleepy Friday, we will post a little historical SP trivia -- but with an on-going echo.

To be clear, Ms. Russo was soundly re-elected, once again this year. And in truth, there is no way to know what drives her long-running, very-high negative votes. I have long-posited that it was her service as Compensation Chair at legacy Schering-Plough, when "Fast" Fred Hassan walked away with over $235 million, for what was roundly, and nearly universally, later decided to be atrocious performance as CEO. Others might attribute the negatives to her stint on the GM board (not exactly a shining-chromed ride) -- or her time at Acatel/Lucent. Who knows?

What is clear is that she persistently receives almost 20 million fewer "yes" votes, and 20 million more "no" votes, than the penultimate least-favored candidate (Mr. Weeks). [It would seem that at least one large institutional holder has chosen to vote against her, consistently. Might it be a union pension fund, from the GM days? Who knows? She does draw high negative votes at GM, as well -- among all the management-supported nominees.] From the just filed SEC Form 8-K:

. . . .Patricia F. Russo | For: 1,909,957,906 | Against: 124,361,135. . . .


Back in 2013, she saw almost 200 million more "no" votes than any other candidate, but this at least 20 million share negative gap has been persistent for five solid years, now. Obviously, a slow news Friday (if this sort of trivia is what I am covering!), going into a long holiday weekend. And. . . I just checked, she draws high negatives at Alcoa -- but not so much at HP, her current "primary" engagement. Fascinating.

In unrelated news (likely accelerating the continuing price wars in Hep C), Kenilworth did see a positive CHMP regulatory opinion -- in Europe, for its Zepatier® (a second to market, lower priced competitor to Gilead's Sovaldi®). Do enjoy the rest -- and warm moist air. . . smile. . . .

Tuesday, May 24, 2016

Merck Investment Vehicle Now Holds Well-Over 10 Per Cent Of OpGen Inc. (With A Cubicin® Gram-Negative Connect)?


This afternoon, Merck updated its SEC ownership disclosures -- of another of its public company investments (nominally held via its Global Health Innovation Fund, LLC). Merck affiliates now own -- and/or hold rights to acquire -- well over 10 per cent of this public company. OpGen bills itself as "a precision medicine company that uses molecular diagnostics and informatics to combat infectious disease." The latest acquisition of rights in OpGen occurred just last Thursday, May 19, 2016. But Merck has had an investment here since before July of 2015.

I strongly suspect that Merck seeks a continued pipeline of information about (and likely eventual license rights to) this company's rapid (just over 30 minute) diagnostics tests, especially as to so-called Gram negative organisms -- like those Merck's Cubicin®, or daptomycin as a chemical name (itself a late 2014 acquisition by Kenilworth) is designed to knock-out. With Cubicin likely subject to generic incursions (due to various patent spats) beginning in July of 2016 -- might this rapid testing protocol eventually be linked to the branded offering, to contiune to keep the branded Cubicin at the fore-front, in US hospital deployments? We shall see.

In any event, the text from OpGen's latest SEC Form 10-K, which accompanies the graphic in the lower portion, at right -- is as follows:

. . . .Our suite of DNA-based products and products in development are intended to provide actionable, precise diagnostics powered by microbial surveillance data. The high resolution Acuitas DNA tests use multiplex PCR to help provide reliable and accurate detection of drug resistance. The QuickFISH tests are powered by PNA technology and provide rapid pathogen ID, typically in less than 30 minutes from a positive blood culture result. The Acuitas MDRO Gene Test is used for determining if ICU patients are colonized with MDROs. Positive samples are confirmed using microbiological methods and the Acuitas Resistome™ test for high resolution genotyping. Test results are maintained in the Acuitas Lighthouse™ data warehouse for subsequent interpretation by physicians and healthcare providers.

We are developing a new disruptive one-hour-testing paradigm that we believe could help address many of the current issues with testing for antibiotic resistance. Results from a new high resolution Acuitas DNA test designed to detect the key resistome profiles of Gram negative organisms will be informed by a smart cloud based clinical database that will provide molecular profiles to aid initial antibiotic selection and clinical decision making. Our proprietary Acuitas Lighthouse profiles distill large amounts of data into one actionable profile. We believe our disruptive approach will be globally applicable and could be an important new weapon in the fight against drug-resistant bacteria. The figure below describes the potential workflow and anticipated results from our new testing approach. . . .


So, yes, I think this OpGen stake/investment dovetails nicely with the Merck-acquired Cubicin franchises (and continued penetration plans for the same). Off to a board meeting and a workout, now. Namaste, one and all. . . .

O/T A Worthy Read, From Our 39th President -- Candidly Assessing Race, In America In 2016. . .


It has been a fairly quiet early news week thus far for Kenilworth, so I will offer up a very worthwhile read -- on the increasingly clear topic of just how dangerous a Trump nomination is likely to be. Dangerous to the cause of fundamental fairness, and equality, in America.

Honestly, I am now openly skeptical that the GOP will survive (as an intact party) in the near term, given the vast chasm he has torn-open, in that party. Like the Whigs, they may well turn out to be. . . . extinct, by 2020. But between now and then, we must do all we can to prevent complacency about this odious reality TV candidate.

And so, since I have mentioned him several times before on this blog -- I will quote our 39th President, here -- and point the readership to the morning's New York Times, on it all. Do go read it -- Mr. Carter is speaking truth, there -- an uncomfortable truth to many white and black alike, but truth, just the same:

. . . .Mr. Carter said the election of Mr. Obama was a hopeful sign, but he added, "I think there’s a heavy reaction among some of the racially conscious Republicans against an African-American being president."

He said recent reports showing high unemployment and incarceration rates among black people, “combined with the white police attacks on innocent blacks,” had “reawakened” the country to the realization that racism was not resolved in the 1960s and ’70s.

He said Mr. Trump had violated “basic human rights” when he referred to Mexican immigrants as criminals and called for a ban on Muslims’ entering the country. . . .


There is much more that is wise and true, at the link -- do go read it.

And before I close -- let me point to a Chief Justice Roberts authored opinion (handed down yesterday), holding (7-1) that a black man's death penalty trial was infected with racism, in the jury selection process -- and thus open to challenge, under the standards of Batson v. Kentucky, even 20 years on -- with newly discovered evidence of bias. That is an encouraging sign, even if Justice Thomas was the lone hold-out -- and clearly wrong -- on the applicable prior common law.

I will now go in search of some light lunch fare, on a flawless spring day, here. . . . Onward!

Monday, May 23, 2016

Merck Foundation Sets Five Year, $15 Million US Cancer Therapies Access Initiative


As the stories of "survivability" -- related to many life threatening cancers -- are being rewritten, almost daily, in the patients' favor -- by these new immuno-oncology checkpoint inhibitors, it makes sense that Merck would use its charitable arm to improve access. Afterall, these are extremely expensive new therapies, and the bulk of people with cancer in the US are not independently wealthy, nor particularly well-insured. So whether you live in Compton or Kennebunkport, it ought to be true -- in a "just" society -- that we (the collective US health care system) will find a way to provide first rate care, and cutting edge therapies, to all equitably.

That is the aim of these awards -- but in candor, much more will be needed, in order to achieve meaningful parity between Harvey, and Hyannis Port. From the press release then, a bit:

. . . ."Despite advances in diagnosis and treatment, access to high-quality cancer care continues to be challenging for some patients in the United States, especially those in vulnerable and underserved communities," said Dr. Julie Gerberding, executive vice president, strategic communications, global public policy and population health, Merck and chief executive officer, Merck Foundation. "We are optimistic that the learnings from the Alliance’s activities will bring forward new approaches in the delivery of cancer care that can be implemented throughout the health care system. . . ."

The Alliance will be supported by the Merck Foundation for up to $15 million over five years. Awardees will be announced in early 2017. . . .


This is a welcome step in the right direction -- but it is only a step. Onward, then -- on a perfect May Monday morning, then. . . smiling. . . .

Sunday, May 22, 2016

O/T: "The Great Society" -- 52 Years Ago, This Evening. . .


It was exactly 52 years ago this evening, that LBJ proposed (and ended up tasking Bill Moyers with) what he called the "Great Society" initiatives. Though many of them were based upon President Kennedy's "New Frontier" initiatives, it was President Johnson who saw them passed into law, after Kennedy's assasination. Mr. Johnson's vision came almost one year to the day after Dr. King's Letter From The Birmingham Jail was first read by most Americans.

As opposed to tax cuts and other preferences for billionaires (Mr. Trump's mantra), both of these Presidents (Kennedy and Johnson) sought a more equitable America -- especially for the nation's lower middle classes -- and those mired in generational poverty. I would clearly add Mr. Obama's name to these two (on health care reform).

Here is just a bit of what the Great Society achieved -- and had LBJ not insisted on escalating his war in Vietnam, he might have enjoyed much more credit, for transforming America into a more just society:

. . . .Between 1964 and 1968 the United States Congress passed 226 of 252 bills into law. . . .

The Food Stamp Act (1964) provided low income families with access to adequate food.

The Economic Opportunity Act (1964) created the Job Corps, VISTA, and other community-based programs.

The Tax Reduction Act (1964) cut income tax rates for low-income families.

The Civil Rights Act (1964) outlawed discrimination in housing, employment, and public accommodations. . . .

Federal funds transferred to the poor increased from $9.9 billion in 1960 to $30 billion in 1968. One million workers received job training from these programs and two million children experienced preschool Head Start programs by 1968. . . .


And so ends our "look back at history" weekend -- but I may revisit these themes, in coming weekends' posts -- to highlight just how much of what is a "more just" America -- that Donald. Trump. Just. Does. Not. Understand. Or. Care. For.

Mr. Trump is manifestly unfit to be President, if he sincerely believes he need not address the issues facing 47 per cent of Americans -- the 47 per cent who struggle every day -- from paycheck to paycheck. He is no one's populist. He is. . . a fascist.

Scottish Nurse Cured Of Ebola In February 2016 Opens Up, On British Television. . .


This is very much a life-affirming story. A triumph as much of human will, as cutting edge bio-science -- Ms. Cafferkey clearly was a fighter, throughout. In fairness, though it is even more a story of what world-class bio-science in the 21st century can do: it can take the near certainty of imminent death right off the table, and all in the space of under an elapsed week, to boot. She is back at regular duty, week in -- and week out.

Even so, she is quite right to feel rather humbled, insofar as she says that she is alive today, because she was admitted to the Royal Free, received those experimental Gilead medications (rushed from the US west coast -- on an overnight transcontinental flight), and was afforded the very best Western medicine had to offer -- all within hours of the re-emergence of Ebola viral loads, around her brain and spinal column. And so, her story is also a reminder -- of all the over 11,300 others who were not quite so fortunate, in Guinea, Sierra Leone and Liberia. Here is a bit of The Guardian (UK) reprint, but do go watch the original ITV piece, at the top of the article:

. . . .Cafferkey told ITV: "I was crying so much to the point that I wanted to scream. I don’t know if I was scared of dying or [if it was] just sheer frustration of being there and wanting out. But the nurses were great; they would just come and sit with me, they would be with me and talk to me. . . ."

"I found it very soothing if they would stroke my hair and things like that to try and soothe me. I probably reverted back to childlike behaviour. I just tried to cope with it."

"I had crazy hallucinations. [I imagined] there were a bunch of Sierra Leoneans and they also had Ebola, but they were outside the tent, and I was saying to the nurse: ‘Treat them, treat them.’ I suppose subconsciously I must have had a degree of guilt, like why I got the best of care, world-class care, and they didn’t. . . ."


And so it goes -- as we await June 9-10 -- and a new all clear in Africa. Love one another.

Saturday, May 21, 2016

Merck Vs. Merck -- First USDC, NJ Scheduling Conference Set: Lanham Act Suit


Regular readers will recall our continuing coverage of the latest federal lawsuit brought by Merck of Kenilworth, New Jersey -- in the federal District court in that state, against the German Merck -- over the use (or misuse) of the Merck name, under a series of antiquated agreements these two companies long ago signed.

I say antiquated -- because they do almost nothing to account for completely borderless electronic global commerce -- in an internet enabled age. For certain, they do not directly address what end-user/consumers (sitting at their screens, or increasingly on their phones) should expect as a consistent, clear and easily discernible line of demarcation -- as to whether one is dealing with, or learning about, the German one or the United States one.

That is so, because the agreements were last amended long before the original DARPA-net evolved into a rich, graphical, seamless world wide web of information and commercial opportunities we now take for granted. The parties just never contemplated such a development. [At least not, it seems, on the consumer side of the equation -- so most of the agreements cover notions about which company may use which naming conventions in which geographies, primarily in promoting themselves to "intermediaries" (pharmacies, hospitals and doctors) -- not so much end user consumers, because DTC advertising barely existed then, as well.]

And so -- the first scheduling conference -- between the parties (on the US version of these fights) is now set for the afternoon of June 2, 2016 -- in Newark:

. . . .Scheduling Conference set for 6/2/2016 at 2:30 p.m. in Newark - Courtroom 2C before Magistrate Judge Michael A. Hammer.

So Ordered by Magistrate Judge Michael A. Hammer on 5/19/2016. . .


Off for a workout, and a breezy afternoon bike ride by the lake. . . .

Keep it spinning in good karma, as 14 years ago tomorrow, the last of the criminals then-living, and responsible for the bombing of the 16th Street Baptist Church in Birmingham nearly four decades earlier -- was finally convicted. It took nearly four decades for justice to roll, in the murders of Addie Mae Collins, Carole Robertson and Cynthia Wesley, all 14, and 11-year-old Denise McNair. Both Michael Blanton and Bobby Frank Cherry are long-dead now, but that sad, twisted story is a clear object-lesson to those who condone violence against people they do not understand, or hate -- for no reason. And I am looking at Mr. Trump -- once again, here. He gives his people "permission" -- and so he is absolutely responsible for their actions, just as the Klan of Birmingham was responsible for the murder of those four little girls. Here endeth the sermon -- but is in keeping with this weekend's theme.

I may devote most weekends to such lower third marginalia -- in direct opposition to the reality TV candidate. He is a dangerous and ignorant would-be demagogue. I will take him lightly, no longer. Any blood-shed he incites, at his rallies -- is on his account. He will burn for it, in eternity -- that is my belief-set.

Friday, May 20, 2016

O/T Civil Rights: Fifty-Three Years Ago, Yesterday -- The New York Post Sunday Magazine, Echoing Through To Today's "Reality TV" Candidate


I meant to get to this, yesterday -- but the time got away. I've run versions of this in 2011, and 2014 -- but because 53 years ago yesterday, most of the world first read the words quoted in blue below -- I'll run it yet again. It never gets old -- it never will become irrelevant. As we listen to a purported billionaire (and reality TV-style purported presidential candidate) tell us to turn our backs on, and shun, so many of our brown brothers and sisters -- these words have renewed, and immediate currency.

Perhaps no one black man in America -- in the last sixty-five years -- has so changed the futures, and fortunes of so many, permanently -- and for the better (and so his portrait will return to my masthead for the weekend):

. . . .My friends, I must say to you. . . . it is an historical fact that privileged groups seldom give up their privileges voluntarily. Individuals may see the moral light and voluntarily give up their unjust posture. . . .

Frankly, I have yet to engage in a direct action campaign that was "well timed" in the view of those who have not suffered unduly from the disease of segregation. For years now I have heard the word "Wait!" It rings in the ear of every Negro with piercing familiarity. This "Wait" has almost always meant "Never." We must come to see, with one of our distinguished jurists, that "justice too long delayed is justice denied."

We have waited for more than 340 years for our constitutional and God given rights. The nations of Asia and Africa are moving with jetlike speed toward gaining political independence, but we still creep at horse and buggy pace toward gaining a cup of coffee at a lunch counter. Perhaps it is easy for those who have never felt the stinging darts of segregation to say, "Wait." But when you have seen vicious mobs lynch your mothers and fathers at will and drown your sisters and brothers at whim; when you have seen hate filled policemen curse, kick and even kill your black brothers and sisters; when you see the vast majority of your twenty million Negro brothers smothering in an airtight cage of poverty in the midst of an affluent society; when you suddenly find your tongue twisted and your speech stammering as you seek to explain to your six year old daughter why she can't go to the public amusement park that has just been advertised on television, and see tears welling up in her eyes when she is told that Funtown is closed to colored children. . . .

[W]hen you take a cross county drive and find it necessary to sleep night after night in the uncomfortable corners of your automobile because no motel will accept you; when you are humiliated day in and day out by nagging signs reading "white" and "colored". . . .

Of course, the above is quoted from the letter from the Birmingham jail -- April 16, 1963. Namaste all. Serve wisely; serve well.





~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

. . . .Anonymous said...

Amazing, heart-felt, "goose-bump" words you wrote. Your writing brought tears to my eyes ... thank you for reminding all of us reading your blog that discrimination should NEVER happen. We are all different, but not one better than another. We all need to treat each other with dignity as that's how we would want to be treated ourselves. Thank you for your eloquent words.

MLK was always one of my heroes when I was a young child. I wrote a paper on him when I was in grade school and, although I didn't understand the ramifications of what he was trying to do at the time, I certainly do today. Young minds are very impressionable. We all need to teach our children about this great man.

January 18, 2011 at 10:53 AM . . .


And so, I urge you my friends (and even those I do not yet count as friends) -- over the coming weekend -- and every day thereafter -- at least for a moment each day -- do serve wisely; serve well. He would have done the same. And he would have said the Donald's "vision" of America. . . is no vision, at all.

Wednesday, May 18, 2016

Immuno-Oncology Races Heat Up: Roche/Genentech Nabs An FDA-Cleared Checkpoint Inhibitor Approval -- Tecentriq®


Well, the immuno-oncology wing of the FDA is popping today. [Of course, there is no formal immuno-oncology wing at FDA -- I just made that up. Smile. it sounds pretty cool though, right?] More seriously, the revamped FDA review process is certainly on full-display, this week. Nicely done, staffers! And it is no exaggeration to call this an emerging three way revolution, in cancer combatting agents -- as of this afternoon. Very gratifying, from a bio-science perspective.

Once again, significantly ahead of earlier time-line expectations, another checkpoint inhibitor immuno-oncology candidate has been green-lighted, by FDA. This new one, called atezolizumab, and branded by Genentech as Tecentriq®, was just approved for a common form of bladder cancers. It is Roche's first entry into this generation of agents -- and while priced on a par with both BMS's Opdivo and Merck's Keytruda -- it is sure to put some heat on Merck, the No. 2 player, in the near term. It is highly foreseeable that some oncologists (with patient consent) will use it off-label, in an experimental fashion, in other cancers. That will likely pressure Merck more than BMS -- as our graphic this morning made plain.

The erstwhile John Carroll (at FierceBiotech) has more of the details, here -- do go read it all:

. . . .The drug will be marketed by Genentech as Tecentriq and sold for $12,500 a month, in parity with rivals Opdivo and Keytruda.

The accelerated OK is based on Phase II data and comes four months ahead of the PDUFA date on the agency’s decision, highlighting once again the FDA’s intense interest in speeding along a new class of cancer drugs that has been making a deep impression on their therapeutic potential.

While Merck and Bristol-Myers made their mark with PD-1 drugs, Roche has been concentrating on PD-L1, a complementary pathway involved in the deceptive game cancer cells play to avoid an immune system attack. And Roche has been paying careful attention in identifying the patients most likely to benefit. . . .


I should also mention that we will expect additional indications, pretty shortly, for the Roche candidate, as well. But this is a high burden cancer, right now. We are now off on foot, in search of soup, on a fine Spring afternoon, awaiting son's arrival by train this evening -- for dinner. . . smile. This is great news for cancer patients. Pax tecum, one and all.

BMS's Opdivo® Clears FDA Four Months Early, In Classical Hodgkin Lymphoma -- Should Extend Lead In Sales


As proof of how the FDA's "new look" -- at approvals -- is rapidly evolving, I would note at the top that this Opdivo® follow-on indication had an expected PDUFA date of September 1, 2016. Let that sink in, a moment.

Yet FDA has approved it overnight -- nearly four months ahead of even that accelerated schedule. Where the benefit is clear, and the potential to prolong quality time, or save lives is evident, it seems the "new" FDA will truly step-lively, to get an approval jacket completed. Of course, in this particular case, Opdivo has already been FDA-vetted in several other cancers, and represents almost no incremental risk profile to the agency, since FDA is well-aware that many oncologists are already using it off-label for cancers (such as cHL) -- where it is not yet formally approved.

I would expect that when Q2 2016 results are available in late July 2016, we will see an additional widening of BMS's sales revenue lead, over Merck's Keytruda®, across all cancers (see Q1 2016 chart, at right). To be sure, there will be lots of revenue for Kenilworth, but it looks like BMS has cemented its hold on the No. 1 spot. Here's a bit, from a press release:

. . . .The U.S. Food and Drug Administration has approved Opdivo (nivolumab) for the treatment of patients with classical Hodgkin lymphoma (cHL) who have relapsed or progressed after autologous hematopoietic stem cell transplantation (auto-HSCT) and post-transplantation brentuximab vedotin.

This accelerated approval is based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. This first approval of a PD-1 inhibitor for cHL patients who have relapsed or progressed after auto-HSCT and post-transplantation brentuximab vedotin is based on a combined analysis of data from the Phase 2 CheckMate -205 and the Phase 1 CheckMate -039 trials. . . .


We are quite encouraged -- and offer Kudos here, to all the FDA staffers.

Now it occurs to me -- in a small plug for my occasional one-off blog -- that while Chagas is not cancer, and even the "New" KaloBios is certainly not BMS, today's news does make the more general point that if FDA wants an effective Chagas treatment, it might well reach approval very rapidly, given that there exists over 30 years of safe, effective use, in various studies' data, on the benznidazole candidate drug -- in Latin America. Off now, for a sunny, breezy walk in. . . smiling widely.

Tuesday, May 17, 2016

USW Local 10-86: By A 3 to 1 Margin, New 4 Year Contract Ratified At Merck West Point, PA


I am smiling quite widely, even though it is well-past my normal bedtime, here. I knew it would come (like Christmas night) -- late. . . but it came. . . .

The USW's Local 10-86 membership has just ratified a new four year agreement -- and the salient terms are below -- do take a look. [With the Obama administration now having to wade into the 39,000 member strong, 30 day strike at Verizon, to get people talking again -- and with no raises offered at present by Verizon, I'd say the Negotiating Committee for USW Local 10-86 did a very-skillful job here, in a very tough job environment. Kudos!]

. . . .Membership this evening ratified the tentative agreement between Local 10-00086 and Merck, Sharp and Dohme. We don’t have the exact count at this time. Unofficially the numbers appear to be 3 to 1 in favor of accepting the proposal.

The contract is for 4 years with raises of 2.5% each year and a signing bonus. . . .

Thank you to all who supported us through a tough process.

President Dan Bangert

2016 Negotiating Committee. . . .


This has to be a relief to many, many of the affected families. And so, a fond goodnight, to all of good will, here. Pax tecum.

Monday, May 16, 2016

Another Supposed "ObamaCare-Ender" Likely Resolved -- By Agreement


This morning, clearly taking pains NOT to issue a deadlocked 4-4 opinion, the United States Supreme Court issued a per curiam (unamimous) opinion in the so-called contraceptive cases -- remanding all of them for additional proceedings in the lower courts -- in the main because the Court itself, at and after argument earlier this year, was able to find a middle ground that both sides said would be a feasible and acceptable fix to the currently articulated dispute. [Update: I should have been clearer, in my commentary, at lunch-time -- a deadlock here would have meant that in five of the six cases, the Obama/HHS's position would prevail, and in the sixth, the petitioners'. And so, had that occured -- in a question of purely federal law, the outcome might have differed, depending on where one lived. That would be an entirely non-sensical result, as the federal law is supposed to be uniform, nation-wide. And so, by clever questioning, and a gentle cajoling of the broad terms for a compromise, the Justices have all but ensured a uniform outcome: the requirement to provide coverage for contraceptives, for all women, at no additional cost, will very-likely now come from the same insurer, even where one's employer is a religious affiliate that objects to such coverage. And that will be the case nation-wide, without the religious affiliate having to file any papers, to claim any exemption. That is a very fine resolution -- as no one on the HHS/Obama side of the table wanted to impinge on sincerely-held religious beliefs -- they simply wanted women to be truly free to choose -- for free.]

As of this morning the Supremes have asked the lower courts to oversee the working-out of a broad compromise. This is very clearly one more affirmative notch in the continuation of ObamaCare -- and a good one. I think five of six appeals level courts held in favor of the HHS (i.e., the Obama) position on the question of access to birth control free of charge, for all women. And the religiously-affiliated employers -- like schools, or hospitals, run by the Little Sisters of the Poor -- have apparently agreed that if they provide insurance that DOES NOT include birth control coverage, but their employees obtain it for free (perhaps even from the same insurer, at the same time, on their own), the Sisters' free exercise rights (under our First Amendment) are not noticably diminished. Here's a bit from the very-learned Lyle Denniston, at SCOTUSblog.com:

. . . .[T]he Supreme Court on Monday. . . cleared the way for the government to promptly provide no-cost access to contraceptives for employees and students of non-profit religious hospitals, charities, and colleges, while barring any penalties on those institutions for failing to provide that access themselves. Thirteen separate cases were sent back to federal appeals courts for them to issue new rulings on the questions the Justices left undecided. One immediate issue is how soon the government can work out the technical arrangements to provide actual access to the contraceptive benefits.

The Court largely shifted to six federal appeals courts the task of ruling on the mandate’s legality — the task that the Court had agreed last November to take on itself in seven of the cases. Five appeals courts had ruled in favor of the mandate, and one had ruled against. All were ordered to re-think those outcomes in the wake of new positions that the two sides in the controversy had made in recent filings in the pending Supreme Court cases. . . .


It is unusual to see the nation's highest court working out settlement proposals, but this is what inexorably happens -- when the Republicans controlling the "advise and consent" process for appointing a new Justice simply shirk their constitutional duties. Our highest court (ever resourceful, on its own quite considerable initiative) then starts to resort to "trial court" level tactics, to avoid a forever riven 4 to 4 deadlock, on a major issue.

In passing, I will also note that Justices Sotomayor and Ginsberg concurred and offered the following admonishment (aimed at one of the federal District courts -- ouch!): ". . .Yet some lower courts have ignored [our] instructions. . . . ("[I]n Wheaton College, Little Sisters of the Poor, and Zubik, the Supreme Court approved a method of notice to HHS that is arguably less onerous than [existing regulations] yet permits the government to further its interests. Although the Court’s orders were not final rulings on the merits, they at the very least collectively constitute a signal that less restrictive means exist by which the government may further its interests"). On remand in these cases, the Courts of Appeals should not make the same mistake. . . ." Ooh! -- that will leave a mark.

It shouldn't escape notice that these two Justices (both women), signing the concurrence are. . . sending a very clear corallary warning, here: when the Court says the free contraceptive provision is constitutional, and thus must be available to all women -- as the ACA of 2010 specifically contemplates -- then that is precisely what must happen [i.e., no more trying to chip away at that right, by saying in effect "oh, some less onerous procedure will do. . . ."] Now you know.

Sending the last college son back north, by train, after a great weekend. . . all smiles here. . . .

Sunday, May 15, 2016

UPDATE: Merck | West Point, PA | USW Local No. 10-86 Contract Ratification Vote, In Just Over 24 Hours. . .


Just as we reported almost six years ago, to the day (same graphic, at right, in fact) -- that a three year agreement was ratified (and another one, in 2013, after a more drawn out process). . . . Tomorrow evening, the rank and file will vote on the new memorandum of understanding.

Given that the USW's website leads with a story on the Verizon workers' strike (members of the Communication Workers of America) now passing its 30th day, and those company-offered terms looking very, very thin -- I do think it would be wise to vote to ratify. As I've said, usually a not perfect agreement is better than a strike. Here "the perfect is the enemy of the good."

. . . .The Ratification Meeting is set for Monday, May 16, 2016 at the North Penn High School. Doors open at 6:15PM. AFTER everyone is properly registered and seated President Dan Bangert will call the meeting to order. . . . [The PDF of the MOU is available to members on the web-site, and has been distributed. . . .]


Onward, on a beautifully clear, if cool Sunday morning. . . . Whoosh!

Saturday, May 14, 2016

High Praise: Pfizer Declares It Shall "No Longer Tinker With The Machinery Of Death"


There is a twisted (and more than occasionally sordid) back-story here -- even though this development has been long-delayed, I won't belabor it. I am all about heaping praise, this fine Saturday morning -- on Pfizer.

So. . . I shout praise -- thank you, Pfizer -- and yes, thank you, Chairman Ian C. Read! The big blue pill company has made an excellent -- and moral -- choice. I applaud it. [My headline above is a quote from a famous Justice Blackmun dissent in a United States Supreme Court death-penalty case, of the last century.] I cannot say enough about how how gratified I am (having worked toward this goal when I was an internal part of this industry) to learn that -- as a now united, unanimous industry -- FDA regulated multi-national pharmaceutical companies have turned their collective back on the small handful of states in our Union that still wish to use pharmaceutical grade injected posions to kill inmates.

Thus the final and effective end of the death penalty in America may be achieved not so much in the courts or legislatures -- but in the lack of supplies: i.e., a court accepted mechanism for implementing it, consistent with all of our existing precedents under the Eighth amendment. Here is a bit of The New York Times on it, overnight (do go read it all):

. . . ."With Pfizer’s announcement, all F.D.A.-approved manufacturers of any potential execution drug have now blocked their sale for this purpose," said Maya Foa, who tracks drug companies for Reprieve, a London-based human rights advocacy group. "Executing states must now go underground if they want to get hold of medicines for use in lethal injection."

The obstacles to lethal injection have grown in the last five years as manufacturers, seeking to avoid association with executions, have barred the sale of their products to corrections agencies. Experiments with new drugs, a series of botched executions and covert efforts to obtain lethal chemicals have mired many states in court challenges. . . .


The arc of the dream that is America inexorably once again bends toward. . . progress -- toward hope. Toward a more civil union, ruled by law -- not men. And for that, I am grateful -- on to a trail-bike ride, and workout, on brisk Saturday then. Onward!

Friday, May 13, 2016

Additional Thoughts -- On Civil Investigative Demands, Out Of Manhattan AUSA's Office: Who Really Is The Target?


To follow up on my earlier report about Merck and J&J's disclosures (in the quarterly SEC filings of each) regarding civil investigative requests, this week -- it occurs to me that both of the drugs which Merck named as being "asked about" by the able US Attorneys in New York, are not on the approved formulary lists, of any major pharmacy benefit manager, or PBM, in the US.

If the very-able Manhattan US Attorneys' line of thought is that Merck somehow paid something improper, to gain favored access/placement on the major PBMs' approved formulary lists, then the request likely would/should have asked about Merck's formulary-favored drugs.

If on the other hand, the concern of the US Attorney has more to do with the power that PBMs increasingly wield, in making formulary approval decisions -- I would think that the US Attorneys' offices would want to see how certain drugs end up getting excluded from that coveted status, and how that might impact both the pricing of other (formulary favored) drugs in the same indication, and overall anti-competitive manuevering, in these US marketplaces. So -- I now reiterate my guess that this may be more about a look at PBMs -- than a look at R&D driven pharmaceutical manufacturers. [CVS and the like ought to be taking notes, here.]

As ever, to be fair, J&J did not indicate which particular drugs its DoJ request asked about (so there is no way to know if J&J's request fits with my hypothesis). And, in any event, I think (if memory serves) Merck has divested at least the Levitra rights, to Bayer (in the Consumer Health sale), post 2014. So again, this is all just idle speculation on my part. But it might well pan out.

Now, onward on a perfectly sunny Friday morning. . . smiling, and awaiting a great weekened. . .

Thursday, May 12, 2016

Yawn. Current Legislators Cannot Sue Whenever They Don't Like The Way The Executive Branch Enforces A Law Passed By A PRIOR Congress


Okay -- in the land of "Condor predicts" tonight -- I will confidently predict that when the SCOTUS gets this House of Representatives v. Burwell DC District Court decision, it will simply reverse without an opinion, or strike it, with an opinion and order holding that (no surprise) Congress cannot (constitutionally) grant itself standing to sue the Executive Branch, simply because the now-sitting House doesn't like the way a prior Congressional enactment is being implemented, by the Executive Branch.

The obvious -- and Constitutional -- answer is that the present Congress must repeal or amend the prior law, not sue to overturn it. The House simply has no standing.

In fact, House Republicans acknowledged that without a specific bill they proposed in 2014, they would have no power to sue, here. And that bill itself failed to pass the Senate -- and so it never became law. Yet, here the House sits today, suing to claim, on putative authority of a later law that did pass, that the prior law's funding provisions weren't specific enough. That later law is itself an unconstitutional abuse of separations of powers doctrines, but no one has bothered to bring a challenge -- because it all seems so silly -- since the SCOTUS will strike the very suit the House now attempts as unconstitutional, as well.

I am unsure whether the SCOTUS will take the trial court's opinion directly, or let it work its way up the chain from the trial court, here. But do rest assured -- without a Republican President, and a NEW law, passed by a subsequent Congress, this whole thing is nothing but political theater. [And I am on record that Mr. Trump will not be our 45th President.] This is all why (in part) the District Court stayed its ruling -- until all appeals are exhausted. Here is the sensible, sane bedrock law on which I base these assertions -- from a case the SCOTUS decided, called Raines v. Byrd 521 US 811 (1997). Here is a bit of the HHS memo of law quoting it, from the current case papers:

. . . .The cost sharing reduction payments are being made as part of a mandatory payment program that Congress has fully appropriated. See 42 U.S.C. § 18082.

In Raines, several Members of Congress challenged the constitutionality of the Line Item Veto Act of 1996, asserting that the statute had injured them by infringing on their power as legislators. 521 U.S. at 816. Although the Members had brought suit pursuant to a provision of the statute that authorized such a filing, the Supreme Court held that the plaintiffs lacked Article III standing. It noted that their claim asserted "a type of institutional injury (the diminution of legislative power), which necessarily damages all Members of Congress and both Houses of Congress equally." Id. at 821. Because the plaintiffs’ "claim of standing [was] based on a loss of political power, not loss of any private right," their asserted injury was not "concrete" for the purposes of Article III standing. . . .

"[T]he authorities appear to hold uniformly that an official’s mere disobedience or flawed execution of a law for which a legislator voted. . . is not an injury in fact for standing purposes. . . . The principal reason for this is that once a bill has become law, a legislator’s interest in seeing that the law is followed is no different from a private citizen’s general interest in proper government. . . ."


Sleep well, now -- and know that this nonsense will not end Obamacare. Not a chance. Smile. . . .

On Q1 2016 Merck Vaccines Sales Growth Stories -- Market Share... Matters.


This FiercePharma story has been out for a little over two days.

I generally find that outlet's reporting to be top notch. I only link to the FiercePharma vaccines item, for a complete record, as I think it suffers from a lack of. . . perspective.

Though closely-guarded as a secret by each of the companies mentioned in the item -- in my opinion, market share (the relative position of Kenilworth, compared to the others mentioned, in each vaccine space) explains the bulk of the "trend" described.

That is, one has lots of room to grow at the sales line, when one is a small player -- and far less room, when one is nearly the largest, or the largest, player. The more salient question -- to my mind -- is what's going on with margins, in each vaccine -- by player? That's my $0.02.

Tuesday, May 10, 2016

Like Several Of Its Large Peers, Merck Has Received A Civil Investigation Request From US DoJ -- Re Pharmacy Benefit Manager Contracts


Among others, Johnson & Johnson disclosed in its latest SEC filings that it too has received this sort of a civil request. Merck disclosed the request it received in its Q1 2016 SEC Form 10-Q, which filed overnight. It matters greatly that this is a civil as opposed to criminal investigative request -- thus presumably, even if it were to turn out badly (which is highly unlikely at this stage), it would not result in debarrment from governmental programs. In general, most government payers expect that they will end up paying at a no worse (nor a better) rate, than a pharma company's best customers. The trick is in figuring out what that might mean, in actual day-to-day practice, with many many layers of contracting -- between the manufacturer (like Merck), and the final buyer.

In the main, it looks like the capable AUSAs in the Southern District of New York are just gathering industry background data (using the big R&D pharma companies as a reference point) -- to sort out how pharmacy benefit managers (via these complex contracts) impact the final price a consumer or insurer or government pays for a given drug. [Note that Valeant and Turing are the subjects of much more far reaching versions of these requests -- and I think the Valeant ones haven't yet ruled out a criminal process.] Even so, the focus may well be on the PBMs, and not on these traditional (i.e., non-Valeant, non-Turing) pharma companies, like Merck and J&J, themselves.

In time we shall see -- but I would not be too terrribly concerned about it all. Merck has responded to several similar requests in the past decade, and not much came of those. Merck is not Valeant or Turing -- that much is clear. In any event, we will watch it -- and here is the operative quote from page 19 of the SEC Form 10-Q, filed overnight:

. . . .The Company has received a civil investigative demand from the U.S. Attorney’s Office for the Southern District of New York that requests information relating to the Company’s contracts with, services from and payments to pharmacy benefit managers with respect to Maxalt and Levitra from January 1, 2006 to the present. The Company is cooperating with the investigation. . . .


Onward -- we will keep you apprised. Definitely smiling now. . . .

Sunday, May 8, 2016

Might BMS's Yervoy® Be Useful -- To Treat Acute Ebola Sufferers? New Research, In Nature -- Points To Hope


Some startling viral epidemiological life-science news just caught my eye on this sunny Mother's Day morning. To be sure, we are a long way from a therapy, here -- and the cost barrier may be insurmountable (as ipilimumab, a biologic, is very very expensive to manufacture and distribute) -- but the finding is well-worthy of note.

A European scientist working with samples of Ebola-infected patients' blood, from Conakry, Guinea, has shown that those who died from the Ebola virus expressed the protein CTLA-4 in high amounts -- not entirely unlike patients who are most at mortality risk -- from melanoma.

So, it would stand to reason that a biologic, like Yervoy® (the BMS brand name for ipilimumab) -- which takes the brakes off of our immune system, to help fight some cancers -- at the CTLA-4 protein site, might be of use -- in combating acute cases of Ebola. Since Yervoy is already FDA approved, the path through animal models, and then Phase II/III studies could be expedited. But any therapy (in Africa) will have to address the economics of delivering it, as well.

Just the same, here's a bit from The Guardian last week, in London (and a link to purchase the article published in the journal Nature) -- but do go read The Guardian article, in full:

. . . .Scientists have identified a key feature in the human immune system that determines whether someone will live or die from Ebola. . . .

A study of blood taken four days after the onset of symptoms in 157 patients in Conakry, Guinea, showed that a significantly high level of a protein known as CTLA-4 - which acts as a brake on the immune system response mounted by the body during an acute infection - indicated that a patient would not survive.

The research, published in the journal Nature, found that Ebola survivors had much lower levels of CTLA-4 and generated an Ebola-specific T cell response. . . .


A very long road yet to travel, from Phase I to a working, economically sustainable therapy in humans, but this is quite exciting -- and welcome news. Onward, on a joyous Mother's Day -- with love, to one and all!