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Hey laser, long time huh? Good to see you’re still around.
I’ve been thinking about all the quotes that I’ve read from Merck executives over the past couple of years and the type of assets Merck was interested in acquiring, and I’m sure that if this trial has positive topline, and Northwest Bio presents very compelling full data at ASCO, that Merck (and other BP) will be extremely interested. I’m not so sure how interested Northwest Bio is in partnering at this point though. I would sure like to be a fly on the wall during those discussions.
I think that manufacturing in the U.S. is ready, and nearly ready in the UK, and Linda is prepared to file a BLA, NDS, and MAA, and take DCVax to market on their own, and is not looking to partner DCVax for glioblastoma. From Linda’s point of view, she could use BP’s money and regulatory expertise, but it may not be worth cutting them in because Big Pharma has little cell manufacturing capabilities, and DCVax would still likely be manufactured by Cognate and Advent who are familiar with, and have automated and industrialized the process for commercial manufacturing. In addition, BP’s large sales and distribution infrastructure is not really needed for a personalized treatment that will initially be distributed through the few hundred neuro-oncologists and medical centers that participated in the trial and are familiar with DCVax, which could easily be handled by a sales force of under 50, perhaps even 25. With an approvable cancer treatment and credibility reestablished, and an uplisting on Nasdaq, I think Northwest Bio will be able to attract favorable financing, which would give Linda considerable leverage if negotiations become serious later this year.
I have wondered why Northwest Bio has not started any of the clinical trials that they have talked about last year. Is it really because they don’t have the financial resources or perhaps another reason? If DCVax proves effective for glioblastoma, I have to believe that Merck would like to run hundreds of trials with DCVax, both as a single agent in multiple indications, and in combination with Keytruda, and they may not have the patience that we investors have had with Northwest Bio’s clinical development plan or pace. From Ken Frazier’s most recent public comments at the JPM Conference, it seems Merck may be able to justify paying a high price for just such a platform technology. Should be interesting.
LOL. Yes good point but I was thinking of Linda's price at $20B+ in the next six months to year would be considered "fully valued" at that point. I still think that most people believe that the development of DCVax would more robust in the hands of Merck. Thinking more about a partnership with Northwest leading the development leads me to believe that Merck would much rather take the whole company and control of development.
This part deserves repeating, and it explains why Merck may be willing to pay $20B+ (or whatever Linda’s number is) for NWBO when they do their due diligence. And by the way, the deal could be structured in a number of different ways including, all cash, all stock, cash and stock, cash and CVR’s, etc.
Kenneth C. Frazier - Merck & Co., Inc. - Chairman, President & CEO
Everything is fully valued out there from everything that we can see. But we have a lot of strength in our balance sheet. We can do transactions as we take the long view. Again, the sweet spot for us has always been the kinds of transactions that are at a stage where we think that we can use our own internal scientific, our development prowess, our commercial prowess, to make those have more value than they do in the hands the people that have them now. And we'll continue to look at them. Even though they're fully valued, that doesn't necessarily scare us away.
Merck & Co Inc at JPMorgan Healthcare Conference JANUARY 14, 2020
https://s21.q4cdn.com/488056881/files/doc_downloads/transcripts/2020/01/MRK-USQ_Transcript_2020-01-13-(2).pdf
Not sure if this has been posted but there’s an interesting discussion at the end . . .
Christopher Thomas Schott - JP Morgan Chase & Co, Research Division - Senior Analyst
Okay. Great. Another kind of core topic has been business development. And I just would be interested in your latest thoughts on the landscape here. It just seems like The Street is generally supportive of Merck building out its pipeline and portfolio. And I was just interested right now what you see the sweet spot is for Merck as we think about commercial versus clinical, as we think about broader platforms versus maybe single product companies.
Kenneth C. Frazier - Merck & Co., Inc. - Chairman, President & CEO
So let me start by saying that we think that business development will remain for us a very big imperative going forward. And the reason we think about that is because we've always been a science-led company. And we always know that there are great opportunities on the outside. So I would say that the way we think about it is what's the next great opportunity in science and how can we get a hold of it in a way that creates value for shareholders.
What we've said is we're not particularly interested in doing a large consolidation-type merger or synergy-driven merger because that doesn't help us over the long term be more effective in innovation. But as we think about bolt-on transactions, we don't really discriminate on the basis of size. We ask ourselves where the next great scientific opportunity is coming from. And we are looking for those, again, in a financially disciplined way, but we're very much focused on them. And last year, we did over 80 transactions. If you include the ArQule transaction, we've spent about $8 billion on those 80-plus transactions. And we're going to continue to be active.
Christopher Thomas Schott - JP Morgan Chase & Co, Research Division - Senior Analyst?It seems like you've also had some success with these partnership type of arrangements? Is there a robust pipeline of opportunities to pursue like
that?
Kenneth C. Frazier - Merck & Co., Inc. - Chairman, President & CEO
So let me start by saying that we think that business development will remain for us a very big imperative going forward. And the reason we think about that is because we've always been a science-led company. And we always know that there are great opportunities on the outside. So I would say that the way we think about it is what's the next great opportunity in science and how can we get a hold of it in a way that creates value for shareholders.
What we've said is we're not particularly interested in doing a large consolidation-type merger or synergy-driven merger because that doesn't help us over the long term be more effective in innovation. But as we think about bolt-on transactions, we don't really discriminate on the basis of size. We ask ourselves where the next great scientific opportunity is coming from. And we are looking for those, again, in a financially disciplined way, but we're very much focused on them. And last year, we did over 80 transactions. If you include the ArQule transaction, we've spent about $8 billion on those 80-plus transactions. And we're going to continue to be active.
Christopher Thomas Schott - JP Morgan Chase & Co, Research Division - Senior Analyst?It seems like you've also had some success with these partnership type of arrangements? Is there a robust pipeline of opportunities to pursue like
that?
Kenneth C. Frazier - Merck & Co., Inc. - Chairman, President & CEO
Well, I have to say that they come along. I think what those opportunities reflect is the flip side of the conversation we have about concentration risk, which is because KEYTRUDA is so foundational, lots of people who are developing lots of other things come to Merck because they're asking the question of whether or not those particular assets are best put in combination with KEYTRUDA. So those are 2 opportunities that came our way, frankly, because people were looking to see whether or not there was a joint development plan with their molecule and our molecule. And we continue to see these opportunities all the time. Roger and his colleagues field lots of requests from people to think about investigating a particular compound or candidate with KEYTRUDA.
Roger M. Perlmutter - Merck Research Laboratories - President
And I would also say that credit to our business development team who are very clever in thinking about, "Gee, how can we expand our impact through these partnership arrangements?" And we're very pleased with what we've been able to do with our colleagues at AstraZeneca and at Eisai. Both Lynparza and Lenvima are doing terrifically well and will do terrifically well in combination with KEYTRUDA.
Christopher Thomas Schott - JP Morgan Chase & Co, Research Division - Senior Analyst?Last question is just I know in the past you've talked about valuation being a challenge for some of the transactions you look at. What latest state
of the land, where are we today with valuation? Is it [everything] at this point? Or is it still balancing?
Kenneth C. Frazier - Merck & Co., Inc. - Chairman, President & CEO
Everything is fully valued out there from everything that we can see. But we have a lot of strength in our balance sheet. We can do transactions as we take the long view. Again, the sweet spot for us has always been the kinds of transactions that are at a stage where we think that we can use our own internal scientific, our development prowess, our commercial prowess, to make those have more value than they do in the hands the people that have them now. And we'll continue to look at them. Even though they're fully valued, that doesn't necessarily scare us away.
Hi again CN. No updates from Larry Smith, but I’m guessing there will be one in a few weeks, maybe after Antares reports their fourth quarter and full year results and the 10-K is filed. BTW- they haven’t cut forecasts, they only provided conservative guidance of about 20% growth. Based on the prescription data, I think Antares will at least break even or earn a small profit this quarter, (a penny) and I anticipate at least modest growth and profitability going forward. The stock price doesn’t always reflect the value of these small companies, but turning the profitability corner is a big positive, and after the recent sell-off, I think ATRS is undervalued. When the uncertainty about the status of Makena and timing of the generic Forteo launch are known, (Teva now says end of 2020 or early 2021) it could give the shares a lift. A little clarity on the pipeline would also help and that should also be known soon. As far as the slowing growth of Xyosted, I think it’s just temporary, and growth will pick back up, but there’s only so much you can do with their limited sales staff and budget.
I’ve always been a long-term investor, but after watching paper profits washed away with these small companies, (ATRS, BLFS & CYRX, etc.) in the last few years, I’ve become more of a long-term trader due to the volatility and games that are played with these stocks. By buying when the price is low (like after the CRL & now) you can then sell individual lots when the price appreciates. Like the old saying goes - If you can’t beat ‘em, join ‘em.
D-2 Warrant expiration: May 2, 2020?
The warrants had a 2-year exercise period, and I believe they became exercisable on May 2, 2018 when the company filed notice that the Company’s certificate of incorporation had been amended to increase the number of authorized shares of common stock. I’m not sure exactly when the company provided written notice though.
Except for the 8,695,652 D-2 Warrants that were issued to Linda Powers in conjunction with her loans to the company in March and April 2018 which had a 5-year exercise period, and expire in May 2023.
Amendments to Articles of Incorporation or Bylaws; Change in Fiscal Year.
On May 2, 2018, the Company filed a Certificate of Amendment of its Seventh Amended and Restated Certificate of Incorporation (the “Certificate of Amendment”) with the Secretary of the State of Delaware, which effected an increase in the Company’s authorized shares of common stock, from 450,000,000 to 1,200,000,000, par value $0.001 per share and an increase in the Company’s authorized shares of preferred stock from 40,000,000 to 100,000,000, par value $0.001 per share. The foregoing description is qualified in its entirety by reference to the full text of the Certificate of Amendment, which is included as Exhibit 3.1 to this Current Report on Form 8-K and is incorporated herein by reference.
https://sec.report/Document/0001144204-18-024749/
Date of report (Date of earliest event reported): December 29, 2017
Exhibit 10.1
THIS WARRANT AND THE UNDERLYING SECURITIES HAVE NOT BEEN REGISTERED UNDER THE SECURITIES ACT OF 1933, AS AMENDED (THE “ACT”). THEY MAY NOT BE SOLD, OFFERED FOR SALE, PLEDGED OR HYPOTHECATED IN THE ABSENCE OF AN EFFECTIVE REGISTRATION STATEMENT AS TO SUCH SECURITIES UNDER THE ACT OR UNLESS SUCH TRANSACTION IS IN COMPLIANCE WITH APPLICABLE FEDERAL AND STATE SECURITIES LAWS.
NORTHWEST BIOTHERAPEUTICS, INC.
CLASS D-2 WARRANTS
No. WD2- ____________ , 2017
This Certifies That , for value received, ____________________________ or its assigns (the “ Holder ”), is entitled to subscribe for and purchase from Northwest Biotherapeutics, Inc. , a Delaware corporation, with its principal office in Bethesda, Maryland (the “ Company ”), such number of Exercise Shares as provided herein at the Exercise Price as provided herein. This Class D-2 Warrant (the “ Warrant ”) is being issued pursuant to the terms of that certain Subscription Agreement, dated __________, 2017, by and among the Company and Holder (the “ Agreement ”).
1. Definitions . Capitalized terms used but not defined herein shall have the meanings set forth in the Agreement, as applicable. As used herein, the following terms shall have the following respective meanings:
(a) “ Business Day ” means a day except a Saturday, a Sunday or other day on which commercial banks in the City of New York are authorized or required by applicable law to be closed.
(b) “ Common Stock ” shall mean the common stock of the Company, par value $0.001 per share.
(c) “ Exercisability Date ” shall mean the date the Company provides written notice to the Holder that the Company’s certificate of incorporation has been amended subsequent to the date hereof to increase the number of authorized shares of Common Stock thereunder and that all other necessary corporate action has been taken to authorize and reserve for issuance the Exercise Shares; provided that the Company shall provide such written notice within five Business Days after such amendment has been effected and all other necessary corporate action has been taken.
(d) “ Exercise Period ” shall mean the period commencing on the Exercisability Date and ending two (2) years after the Exercisability Date.
(e) “ Exercise Price ” of this Warrant shall be Thirty Cents ($0.30) per share.
https://content.edgar-online.com/ExternalLink/EDGAR/0001144204-18-000828.html?hash=ea58efbb168500a865cc410fdcc0f9a3557928c6bcbecf5dec6cfb36c7516b1d&dest=TV482665_EX3-1_HTM#TV482665_EX10-1_HTM
Thanks for the post iwasadiver. I don’t usually like to speculate either, but it’s interesting to hear your thoughts. I was expecting a shareholder meeting notification sometime this week, but thought it would be scheduled in early March. So reading that the meeting won’t be held until April 18th, and that they expect it to be “interesting” is definitely intriguing. So why wait, right? I kind of doubt that it has anything to do with the timing of the 10-K. Not much to really discuss about the financials. I’m also not so sure that they would reveal a more definitive timeline unless it had been revealed already in a public release.
It sounds to me like they will have something to talk about, and the only thing I can come up with is data lock and topline. They may not know exactly how long it will take, but they seem to have been hinting that they know when it will be. So, by pushing the ASM out two months, they could announce one or both before the meeting. This would also nicely coincide with the late-breaking abstract deadline for ASCO on March 18th, and then full data revealed in a peer-reviewed setting at ASCO. This may just be wishful thinking, but I’ll throw it out there . .
Dr. Keyoumars Ashkan - minute 45:44
Good afternoon everybody. Can you all hear me? I’d just really like to start out by saying how humbling it is to sit there and listen to our patients talking. Because as a clinician, everything I do, and I’m sure that this is true for the other clinicians as well, is for, and only for… the patients. Also this crystalizes what medicine is all about. Medicine is a science, but it’s equally an art, and patient experiences, patients and what they go through, really, really matters. So that’s a very, very hard act for me to follow for the next five minutes, but I shall try.
So I wear two hats. I’m a neurosurgeon, a clinician working in Kings College Hospital in South London, I deal with patients with glioblastoma day in, day out. I’m also a scientist, and a neuroscientist that obviously does research and understands research. So I fully recognize the limitation of the data that we published earlier this week - and the nice presentation that Marnix showed. What we have at the moment are interim data. And of course, we have to wait for the mature data to come out, for the data to be unblinded until we can make the final conclusions. But the clinician in me cannot help being excited about what we have here. Day in, day out, I sit in the clinic and I see patients with glioblastoma, and I go through the same things over and over again. Limited treatment options: surgery, radiotherapy, chemotherapy, and then ending the conversation with a poor prognosis. So anything that gives us hope, and if it is cautious optimism at this stage, is very, very welcome.
On a personal level, I’ve been involved with DCVax for the past seven years or so, and it’s been very interesting times. Because as I say, I work in London, so UK time and US time are very different. So my days are spent doing my clinical work, operating, seeing patients, etcetera. At nights, I’m on conference calls to the states for research. So again, it’s very nice to see that after seven years of sleepless nights, it hasn’t been wasted either. And you know, the data that Marnix presented also really very much is in harmony with my own personal experience, both in the trial and also outside the trial. So I don’t think it is a one-off. I think it is what we are actually seeing. And I really look forward to the eventual final data when it comes out.
Let’s face it. We work in a field in which advancements are very slow. Really, the last very major development in the field of brain tumor management was over a decade ago when Temodor, as you call it, Temozolimide, as we call it, [??] pathway. And we haven’t really had anything that fantastic to get really excited about. So I think, just about, I think, I think, I hope, we are there with this… DCVax.
So why is GBM difficult to treat, and why do I think DCVax is special? The answer is very complex but actually very simple. It is… GBMs are difficult to treat because of the genetic heterogeneity. And Marnix has already alluded to that. So we now know in a patient, any patient and any given one time, the same tumor, different locations within the same tumor have different genetic characteristics; and therefore, they can behave differently. Now imagine that amongst different patients, and also imagine that from across time, when the tumors recur. So really, in order to be able to cope with that genetic heterogeneity, we need two things, and that’s, I think, what DCVax brings into the equation. So when we produce DCVax, we need as much of the tumor as possible. So that’s what we do. We go in there and take as much of the tumor as possible and that gives us access to the fullest spectrum of the antigens, proteins, all those things which are related to the genetic diversity of the tumor. And therefore, when we make the vaccine apheresis and that gets rid of that all sampling errors. We have the whole lot of the tumor. And I think that’s one of the key aspects of DCVax. The other important aspect is that stimulates the immune system… it works with the immune system. And to my mind, the immune system is the most intelligent system we have available in the twenty first century. Why? Because over millions of years, it has evolved to be able to cope with all those diverse insults that nature throws our way. Different bacteria, different viruses… our own immune system can adapt to cope with that variability. And what better to stimulate the immune system against the genetic diversity of glioblastomas? So I think the science makes sense.
So DCVax is personalized, but also has got other advantages. From my point of view, as a clinician, the first thing we learn in medical school is first, do no harm. And you’ve seen the risk profile based the available data that Marnix presented looked good. And also, it’s very easy to deliver. It’s an intradermal injection so actually it’s quite easy to access and to do for the patients.
So I think what we have at the moment… it is interim data. We’ve got to be very cautious. We have to interpret it within those boundaries. But I think it is something to be hopeful. But there is still a lot to do. We have to work towards unblinding this study. I know Marnix explained the reasons that it’s been delayed, but as a clinician, I’m still going to push for it, because I think that’s very important. That’s what we need to be able to understand the impact of this. So I shall continue asking day in, day out.
We also have to work with the regulatory bodies, and we probably ought to do that now, right, not even waiting, because we want this to be available to all the patients. Again, while it’s very nice about these studies… yes, those patients who are in better prognostic groups are going to benefit more… but there is a benefit to all patients. We want this available to absolutely everybody. And absolutely everybody cannot afford everything. So the cost needs to be brought right down, and again, I’m going to be fighting for that, because I want this available to all my patients. We need to get the prices down, work with the regulatory bodies, approve it at a price which patients can afford. And I think that’s incredibly important. And you know what? I think you have to do all that… why? Because we owe it to these guys [points to the patients on the stage]. Thanks very much.
Transcription of ASCO 2018 video - courtesy of sentiment_stocks
INSIGHT: The SEC/FDA Nexus: Best Practices for Publicly Traded Life Sciences Companies
Nov. 19, 2018, 9:43 AM
Pharmaceutical companies and medical device companies frequently must determine what (if anything) to communicate to investors about key developments in clinical trials or the Food and Drug Administration’s (“FDA’s”) regulatory review process. This decision is often complicated because a disclosure may be required even in instances where a company has incomplete information. A life sciences company may, for example, be uncertain about the status of the FDA’s regulatory review, have partial results from a pivotal clinical trial, or have reports of serious adverse events in the absence of confirmatory evidence. In these situations, a company may conclude it has to say something to investors. Determining what to say, however, requires great nuance to ensure that meaningful information is relayed while clearly describing the limits of the company’s knowledge.
Statements made by life sciences companies are closely scrutinized by the Securities and Exchange Commission (“SEC”) and Department of Justice (“DOJ”). These agencies recognize that investors often base their investment decisions on disclosures relating to clinical trials and the status of the regulatory review process. That is particularly true when a company’s financial well-being is dependent on one developmental product, in which case even relatively routine regulatory developments may be deemed “material” and require disclosure.
The SEC and/or DOJ will open investigations if they believe life science companies may have intentionally deceived investors. These inquiries are often aided by a key inside source: the FDA. The FDA will know exactly what it communicated to the company about its regulatory review. Since 2004, in fact, the FDA and SEC have had a coordination mechanism that enables the FDA to make referrals to the SEC if, “in the normal course of their activities, they come to believe that a company may have made a false or misleading statement to the investing public.”
SEC and DOJ investigations present far greater risk than ordinary commercial litigation. These entities have broad (although not unlimited) subpoena power to gather documents and question witnesses. And the consequences of enforcement may be severe: large fines for the company and its executives, bars on service as a director or officer at a publicly traded company for a period of time and, in extreme cases, criminal prosecution including potential jail time.
Examples of SEC and DOJ Enforcement Actions that Illustrate Challenges Faced by Life Sciences Companies in Making Disclosure Decisions
The SEC’s investigation of Clovis Oncology, Inc. (“Clovis”) highlights the challenges that a company faces when making disclosures about ongoing clinical trials. The following factual summary reflects the SEC’s allegations, which Clovis has neither admitted nor denied. In 2015, Clovis was in a race with a competitor to receive approval from the FDA for a drug designed to treat a particular type of lung cancer. The competitor had already disclosed that its drug had a confirmed 63% efficacy rate. In May 2015, Clovis told investors that its drug had an efficacy rate of 60% – but Clovis did not disclose the data were unconfirmed. Investors believed that Clovis’ disclosure was good news because it appeared to show that the efficacy rate of Clovis’ drug matched that of its competitor. In July 2015, Clovis’ executives were told that the unconfirmed efficacy rate was 42% and the confirmed efficacy rate was 31%. Based on prior experience, these executives hoped that the efficacy rate would increase with the passage of time. Clovis nonetheless again referenced the 60% efficacy rate in solicitation materials for a $298 million stock offering. In November, 2015, the FDA informed Clovis that it believed the efficacy rate was in the 20% range. Clovis nevertheless used the 60% efficacy figure at an investor conference and did not tell investors that the FDA believed the efficacy rate was significantly lower.
Clovis ultimately disclosed that the drug’s efficacy was 28%. Clovis’ stock fell 70% on this news, and the SEC opened an investigation. Under the terms of a settlement with the SEC, Clovis agreed to a $20 million penalty and two executives agreed to significant monetary penalties.
In another recent case, the DOJ’s criminal prosecution of InterMune and its CEO highlight that a company must consider not only what clinical trial data it discloses but how it characterizes that data. As addressed below, the DOJ’s prosecution was based on a disclosure that was literally true but allegedly omitted key information about how the company reached its results. Specifically, InterMune sought FDA approval to use Actimmune to treat idiopathic pulmonary fibrosis. The clinical trial, however, failed to achieve the desired endpoint because there was no statistically significant difference between patients who took the drug and a placebo. The company issued a press release touting that the drug reduced mortality by 70% for a specific subset of patients, those with “mild to moderate disease”; the press release also acknowledged that the clinical trials had failed to meet the primary endpoints. The DOJ took the position that the press release was fraudulent – notwithstanding that it was technically accurate – because the press release did not explain that the subgroup of patients was not identified until after the trial. The DOJ argued that once a clinical trial failed to meet primary endpoints, the company should not have made claims about efficacy in patient subgroups that were identified post-trial. On the basis of this press release, the DOJ brought fraud charges against InterMune and its CEO, W. Scott Harkonen. InterMune agreed to a $37 million fine and entered into a deferred prosecution agreement. Dr. Harkonen was convicted of wire fraud and was sentenced to six months of home confinement.
Best Practices for Life Sciences Companies to Reduce SEC and DOJ Enforcement Risk
Life sciences companies should have protocols in place to ensure that all statements about significant developments in clinical trials and the regulatory approval process are carefully reviewed for accuracy. It may be prudent for such statements to be reviewed by an interdisciplinary team that includes members of the company’s senior executive leadership, investor relations, scientific experts, regulatory experts, in-house counsel and, where appropriate outside counsel with expertise in both securities and FDA law.
A. Statements About Clinical Trials
* Make accurate statements about clinical trial data. A company should not make statements about clinical trial data that are contradicted by the underlying data. If the FDA has a different interpretation of the data, the FDA’s differing interpretation under many circumstances should be disclosed to investors.
* Provide appropriate caveats regarding clinical results. Statements about clinical trial data should include proper qualifications so that investors can make their own informed judgment about the significance (or lack thereof) of the applicable data. This issue is of particular concern to government enforcers, as evidenced by the SEC’s allegation that Clovis acted improperly by not disclosing that the efficacy rate was unverified and DOJ’s allegation that InterMune and its CEO committed fraud by not disclosing that the patient subgroup highlighted in the press release was not identified until after the clinical trial. Similarly, a company may risk an enforcement action if it touts a product’s safety or efficacy without disclosing negative test results.
*
* “Top line” results should not overstate the outcome of a clinical trial. A company faces a particular challenge in a situation where it has “top line” results from a clinical trial but the company cannot yet disclose the underlying data. A company risks the allegation that a “top line” summary omitted significant details, e.g., that notwithstanding that the primary endpoint was met, the drug or device provides only modest benefits. A company should consider: (i) whether it has conducted sufficient analyses to reach a “top line” determination; (ii) whether the company is required to disclose those “top line” results to investors; and (iii) what the company should say about them. If the company determines that disclosure is required, it should include appropriate caveats regarding the company’s state of knowledge. Further, to the extent possible, a company should avoid putting itself in a situation where it may be alleged to have overstated a product’s benefits.
*
* Ensure that clinical trial data is accurate and reliable. A company risks fraud allegations if it discloses a favorable clinical trial outcome but knows (or should have known) that the underlying data may be unreliable. Ensuring data accuracy and integrity is a complex task and a full discussion is beyond the scope of this article. A company should generally ensure that clinical trials are conducted by independent researchers who do not profit if a trial is successful. Nevertheless, a company is ultimately responsible for all aspects of a study and therefore should consider establishing mechanisms such as review committees, periodic audits or independent reviews designed to identify potential errors or actual misconduct. Additionally, all adverse events should be properly reported to the FDA.
*
B. Statements About the Regulatory Review Process
* Evaluate the need to disclose negative information obtained from the FDA about a pending application. Companies often obtain negative information from the FDA – particularly with regard to drug or device development. Such information may, under some circumstances, be material and may need to be disclosed immediately. When a company becomes aware, for example, that approval may be delayed, that a product is not likely to be approved by the FDA or that the approval status has otherwise changed, it must be cautious about disclosing inaccurate or incomplete information.
*
While there is no requirement to disclose exact copies of communications from the FDA, companies should assume that the SEC or DOJ will carefully compare what a company has been told by the FDA with what the company has told investors. Any material discrepancies could form the basis of an allegation that the company has intentionally defrauded investors. Andrew Ceresney, the former SEC Enforcement Director, emphasized the importance of accuracy regarding communications with the FDA: “Accuracy of reporting in your dealings with the FDA is critical to getting investors the information they need. FDA dealings and approvals are the lifeblood of your business and are so important to investment decisions.”
* Analyze public statements that are predicated on assumptions about the outcome of the FDA’s regulatory review process. A company should carefully analyze statements about the company’s business initiatives that are based on unspoken assumptions about the status of regulatory review. For example, a company should not provide unqualified projections of a product’s sales starting in one year if communications from the FDA suggest that it will take at least 18 months for the product to be approved.
*
C. Statements About Post-Approval Developments
* Ensure that statements about a product are accurate even after FDA approval has been obtained. The FDA may inform manufacturers that it has concerns about products that are already on the market. To the extent such concerns raise a potential material risk that the FDA may expect a company to conduct a recall or cease marketing the product entirely, such communication should be taken into account as appropriate when the company is making public communications about the product. Additionally, a company should implement appropriate safeguards to ensure that its products are not being marketed off label. Not only is off-label marketing potentially illegal in its own right, but a company risks the allegation that it improperly led investors to believe that product sales were legitimate and likely to continue, when in fact a significant portion of sales were the result of unlawful promotional activities.
*
* Evaluate the need to disclose FDA inspection results. The mere fact that a company has been inspected by the FDA is routine and generally is not material. If, however, the FDA informs a company of serious manufacturing or regulatory problems, a company must evaluate whether a disclosure is required. A materiality determination typically will depend on varied factors such as the size of the company, the number of inspections conducted relative to the number of deficiencies found, the facts known to the company, the company’s history with FDA, the agency’s language in notifying the company of the problem and the likelihood and severity of sanctions. Thus, if a company believes that there is a high probability that the inspection will result in sanctions and that the sanctions would have a significant impact on the company, then the inspection results may be material. By contrast, the results may be immaterial if the company reasonably determines that any deficiencies identified are currently being – or already have been – remedied, the cost of remediation is not significant, and the company is unlikely to face costly sanctions.
* Evaluate the need to disclose adverse events. There is no obligation to disclose every adverse event report because it is well recognized that the existence of an adverse event does not necessarily mean that the product caused the event in question. However, adverse events could become material if they are serious and unexpected, there is statistically significant data showing that the product causes the reported event, or even if there is data that shows a plausible causal link between the product and the event. Even if a company determines that adverse events are immaterial, it should consider whether any affirmative statements made by the company are questionable in light of information available to the company at the time statements were made. If adverse events ultimately trigger a public relations crisis, the SEC and DOJ may analyze whether a company’s statements about a product’s safety or efficacy were consistent with its knowledge about adverse events at the time that the statements were made. If there is a significant discrepancy between what a company said and what the company knew, it may be subject to enforcement actions for misleading investors. Additionally, the DOJ may allege the company committed mail or wire fraud by misleading consumers.
D. Additional Practical Pointers for FDA-Regulated Companies
* Avoid selective disclosure. Regulation FD requires domestic public companies, and persons acting on their behalf, to make simultaneous public disclosure when discussing material nonpublic information with certain market participants. For example, in 2003, Schering-Plough and its CEO settled charges brought by the SEC alleging violations of Regulation FD based on disclosure by the CEO of material nonpublic information about the company’s earnings prospects to institutional investors. Most public companies either have a stand-alone Regulation FD policy or incorporate the substance in another policy addressing corporate communications. Publicly traded FDA-regulated companies should review compliance with Regulation FD and their own communications policies with respect to material nonpublic information about clinical trials, the regulatory review process and post-approval developments.
* Consider whether to update existing disclosures. The full slate of corporate disclosures – from existing risk factor disclosures in annual reports on Form 10-K and quarterly reports on Form 10-Q, to company website disclosures and investor presentations – should be reviewed against new material nonpublic information to assess whether the company has a duty to update. This duty can be triggered by, for example, an upcoming periodic SEC report or a securities offering.
* Confirm compliance with applicable corporate governance policies and procedures. A variety of existing company policies (e.g., insider trading policy, disclosure policy, corporate governance policy, code of business ethics) are often implicated by new material nonpublic information. For example, the general counsel may be required to close the window for trading in the company’s securities. A key question posed in any SEC enforcement action is whether the company’s governance policies and procedures were adequate and whether the company acted in compliance.
* Always use precise language to the extent possible. Press releases and other public statements should be carefully scrutinized to reduce or eliminate ambiguity. If a press release can create confusion or be misinterpreted, the likelihood of an SEC or DOJ enforcement action will be increased.
* Consider whether “safe harbor” language is sufficiently detailed. A company may choose to make forward-looking statements, which are protected under the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995 – provided that such a statement is accompanied by meaningful cautionary statements identifying important factors that could cause actual results to differ materially from those in forward-looking statements. In many cases, safe harbor language may require specific and substantive information about particular events, including specific risks that may affect whether predictions materialize as anticipated. By contrast, boilerplate warnings that are true of every drug or device, e.g., that FDA may not approve a drug, may be insufficient.
* Ensure that short- and long-term predictions are reasonable. SEC and DOJ generally understand that the FDA approval process is subject to inherent uncertainties, and accordingly a prediction about FDA approval or clinical trial results is not considered to be false merely because the prediction does not come to fruition. Instead, enforcers will generally analyze a prediction by considering whether a company had a reasonable basis for making the prediction at the time the prediction was made.
* Ensure that public statements are reviewed by both FDA and SEC counsel. The interplay between FDA and SEC legal and regulatory requirements makes a multidisciplinary review essential to ensure compliance with both agencies’ legal standards. Ideally, FDA and SEC counsel should work in tandem to ensure that there is a seamless review of applicable legal issues.
For a life sciences company, there is no time like the present to evaluate whether it has processes in place to ensure that statements regarding clinical trials and regulatory review are carefully analyzed for accuracy. These processes should be periodically updated to include precautions against pitfalls that may have been experienced by the company or other life sciences companies that were the subject of enforcement actions. Further, when reviewing public statements about these issues, the best advice is to err on the side of caution when there is meaningful uncertainty regarding the outcome of a clinical trial or the regulatory review process. Taking these steps can go a long way towards minimizing the risk of enforcement.
https://news.bloomberglaw.com/securities-law/insight-the-sec-fda-nexus-best-practices-for-publicly-traded-life-sciences-companies
Johnni, I’m sorry to hear about your husband. I’m not religious but I’m sending my positive thoughts.
I agree with the advice from sentiment_stocks. This is the detailed tumor tissue collection method Northwest Bio’s DCVax-L recommends: http://virtualtrials.com/pdf2018/dcvaxfreeze.pdf
Brain tumor tissue is commonly preserved by the FFPE method (formalin-fixed paraffin-embedded). Preserving the tumor by freezing is preferable so it can be tested to determine which chemotherapy or immunotherapy agents might work best. A company that provides this service: Store My Tumor https://storemytumor.com
The tumor tissue should be tested for genetic mutations such as MGMT status, H3 K27M (or mutation of the H3F3A gene), IDH1 mutation, EGFR mutation/amplification, etc. These are very important and can change your treatment plans. If MGMT is unmethylated, Temodar has less of a chance of helping and this opens the door to other treatments instead. If H3 K27M (or H3F3A), EGFR, IDH1 or other genes are mutated, there are targeted treatments available. It is best to discuss the tests with your surgeon prior to surgery - if they do not offer these tests routinely, you can ask them to send the sample to a lab. Two companies that offer this testing are Caris Life Sciences https://www.carislifesciences.com and Foundation Medicine https://www.foundationmedicine.com
You might also contact some of the brain cancer advocacy groups who know about other promising treatments and available clinical trials and can help with a number of issues like getting insurance reimbursement for off-label use, support groups, etc.
Brain Cancer Advocacy Groups
Musella Foundation (Al Musella is very knowledgeable about various treatment options and clinical trials)
https://virtualtrials.com/index.cfm
National Brain Tumor Society
https://www.abta.org
American Brain Tumor Association
https://www.abta.org
Checklist for the Newly Diagnosed
https://virtualtrials.com/Checklist_for_the_Newly_Diagnosed_treatments.cfm
senti, I'm envious of your meeting. Thank you for sharing this information (and follow-up) with the board. You are awesome!
Cheers Hb, I knew NWBO wasn’t in the top 10, but wasn’t sure if it was a smaller holding. I think there may have been more front-running short sales of his former assets again as his other fund (WPCT) assets are also being liquidated.
WPCT update reveals ‘disappointing’ progress as Schroders takes over
By Jessica Tasman-Jones, 16 Dec 19
Announcement comes as Link reveals only 56% of Woodford Equity Income has been liquidated
https://portfolio-adviser.com/wpct-update-reveals-disappointing-progress-as-schroders-takes-over/
The Woodford Patient Capital Trust has been accused of slow progress on the sale of investments as it hands the reins to Schroders and rebrands as the Schroder UK Public Private Trust.
The board revealed on Friday its credit facility had been reduced from £150m to £112.9m, the latter being the amount currently drawn. Gearing on the investment trust, which as of Monday trades under the ticker SUPP, is 23%, according to the Association of Investment Companies.
Investment trust takes its time selling down companies
JP Morgan Cazenove said in a note “this implies there has been no further progress in terms of selling investments from the portfolio” since the last update on the credit facility three months ago.
The amount drawn from the credit facility was £111.1m, according to an update on 26 September. That was down from £116m at the end of June due to the sale of two unquoted investments, ADV and Ultrahaptics.
Portfolio Adviser is waiting for a response from the investment trust about why the amount drawn from the credit facility has increased by £1.8m since September.
The progress revealed in the latest update was “a little disappointing”, said JP Morgan Cazenove.
Slow progress on the investment trust portfolio mirrors the lack of sales in the illiquid and unquoted holdings in the Woodford Equity Income fund, which Blackrock and PJT Partners are responsible for selling as part of the fund’s wind-down.
Authorised corporate director Link revealed on Friday that while 80% of the liquid portfolio had been sold, 44% of the portfolio is yet to be liquidated. Like the Woodford Patient Capital Trust, the open-ended fund has also now been rebranded to the LF Equity Income fund.
Link update reveals 80% of liquid Woodford stocks have been sold
By Jessica Tasman-Jones, 13 Dec 19
https://portfolio-adviser.com/link-update-reveals-80-of-liquid-woodford-stocks-have-been-sold/
Link has revealed it has freed up £1.65bn from the liquid assets in the Woodford Equity Income fund but is keeping mum on progress in the sale of unquoted stocks in the portfolio.
In a letter to unitholders, which coincides with the results of UK general election, Link said Blackrock, which is responsible for the liquid part of the fund, has sold 79% of the portfolio it is responsible for. The cash realised has been re-invested in FTSE 100 index instruments, money market funds, government securities and commercial paper with short maturity date.
The remaining 21% of the portfolio is in “generally less liquid stocks than those assets sold so far”, managing director Karl Midl told Woodford Equity Income investors, who have been trapped in the fund since June.
The authorised corporate director provided no detail on progress in the unquoted holdings that are being managed by Park Hill. “We and Park Hill continue to explore opportunities for selling the Portfolio B assets while maximising the return for investors. However, at this stage we are unable to confirm when these assets will be sold. “We will provide further updates on the progress of the sale of the remaining assets and dates for the subsequent capital distribution to investors until the process is complete.”
The Blackrock sales in total only represent 56% of the Woodford Equity Income fund.
ASI may be the source of the recent selling pressure:
Aberdeen Standard reveals radical overhaul of Woodford fund ahead of reopening
New managers have dumped nine of Woodford’s top 10 stock-picks and pivoted the Income Focus fund toward larger, more liquid companies
By Mark Cobley February 12, 2020 2:18 pm GMT
https://www.fnlondon.com/articles/aberdeen-standard-reveals-radical-overhaul-of-woodford-fund-ahead-of-re-opening-20200212
Aberdeen Standard Investments, which took over Neil Woodford’s £250m Income Focus fund at the end of last year, has pivoted the fund away from consumer stocks and financials and dropped many of his largest holdings.
ASI updated investors on the management of the fund on 11 February, ahead of its official reopening on the 13th, when retail buyers will be able to buy in and out again.
The duo now in charge of the portfolio, Thomas Moore and Charles Luke, said they had diversified its sector bets, improved its liquidity and “sold down structurally challenged companies”.
The fund has underperformed its benchmark during the transition period, gaining 1.4% between 31 October and 12 February while the FTSE All-Share gained 5.1%, according to figures from FE Analytics. The new managers said this was partly due to the costs of shifting the portfolio, and partly due to the “poor performance of certain inherited holdings”.
Only one of Woodford’s top 10 holdings has made it into the new portfolio, with notable casualties including doorstep lender Provident Financial and housebuilders Barratt Developments and Taylor Wimpey, whose shares have been weighed down by Brexit-related fears for the UK economy. Moore and Luke have held onto Bovis Homes, however, Woodford’s second-largest pick, now known as Vistry Group after an acquisition announced in January.
One of Woodford’s top holdings, the Honeycomb Investment Trust, proved a particular challenge for the new managers to sell, they said. “This is a highly illiquid stock with a significant ongoing overhang from large shareholders perceived by the market to be likely sellers. As such, it was necessary to place the stock at a discount to the prevailing market price.”
They also picked out retailer Card Factory as another poor performer, which had been in Woodford’s top 10. The stock “contributed circa 1.23% of [the fund’s] underperformance as a result of a profit warning due to poor Christmas trading — a development which reinforced our conviction that this stock did not merit an ongoing place in the portfolio”.
Moore and Luke have significantly diversified the portfolio and increased its liquidity. Before the transition, 70% of its money was held in large and mid-cap stocks, a spokesman said, with the remainder held in harder-to-sell smaller companies. As of now, that proportion has increased to 97%.
Last October, 35% of the money in Woodford’s fund was invested in consumer-goods companies — a category that included the housebuilders — and another 35% was invested in financial stocks, like Provident, and UK banking group RBS.
Under Aberdeen’s management, the new-look fund has 18.2% of its money in financials, with a notable exposure to UK merchant bank Close Brothers, and 17.6% in consumer discretionary stocks. It has also put a big bet on industrials, with 20.8% of the portfolio — a sector where Woodford had investments worth 13% of the fund.
In their update, Moore and Luke wrote: “We see a range of well-capitalised UK domestic stocks with the potential to perform strongly following a long period of subdued investor sentiment, including Close Brothers, SSE and Assura.
“Alongside these domestic holdings, which are now all held in the portfolio, we see potential for internationally exposed stocks with robust dividend prospects such as Coca-Cola Hellenic, Tui Group and Ashmore. Similarly, these three companies are now part of the repositioned portfolio.”
In a statement alongside Aberdeen’s, the fund’s administrator Link Fund Solutions confirmed the Income Focus fund would reopen to dealing on 13 February, as expected. Investors have been able to submit requests to buy and sell shares from 12pm today.
Hmmm probably someone pretty ignorant. Oh yeah, it was Adam a year ago when he was “schooling” Bigger and Rago :) Now I wonder who said DCVax is outdated.
@adamfeuerstein
Replying to @biggercapital and @rago_carlo
Ya, unfortunately for $NWBO, this is not the case. As I’ve explained to you before, DCVax is very old cancer vaccine technology, long ago made obsolete. Seriously, the work Gritstone and others are doing w/ neoantigens is very interesting, worth looking at.
11:31 AM · Feb 22, 2019
Thanks, good info as usual Lykiri. Glad to hear Advent is evaluating it. This closed, automated system is cost-effective and exactly what the FDA and other Regulatory Agencies encourage companies to use for commercial production. And I believe it only requires a grade-B clean room, which Advent will have.
Automated Reproducible Dendritic Cell Production
August 1, 2019
https://www.genengnews.com/sponsored/automated-reproducible-dendritic-cell-production/
Antigen-presenting dendritic cells (DCs) act as messengers between the innate and the adaptive immune systems. Present in tissues that are in contact with the external environment, such as the skin, the inner lining of the nose, lungs, stomach, and intestines, DCs can also be found in an immature state in the blood in very low concentrations (<1%). For in vitro studies, they are typically generated from monocytes.
DCs are indispensable in immunology and immunotherapy research on cancer and infectious diseases, as well as autoimmune disease and transplant rejection. As key elements of personalized vaccines for cancer and infectious diseases, they advantageously generate immunological memory and allow for autologous or allogeneic therapies, which have demonstrated promising results in the clinic.
Despite heavy investment in R&D involving DCs, under-developed and inefficient manual protocols for DC generation lead to batch-to-batch variability and inconsistencies and contribute to increased costs and research slowdowns.
The current gold-standard method for generating DCs from monocytes has 11 laborious manual steps involving 15 hours of technician time. Steps include static culture and stimulation with cytokines contained in culture media using multiple T-flasks or well plates.
To address this manufacturing dilemma, market-leading Corning entered into an agreement with Flaskworks to commercialize MicroDEN, an automated fluidic system that allows for differentiation of monocytes into DCs utilizing continuous perfusion of differentiation media.
“Using an automated, perfusion-based process such as MicroDEN for dendritic cell production eliminates six manual steps, reduces the risk of contamination, and efficiently produces repeatable results in less time,” said Elizabeth Misleh, senior product line manager, bioprocess, at Corning Life Sciences. “It also eliminates the variability that can result from different levels of technician proficiency.”
The closed system provides consistent yields and requires only three hours of technician time during the week-long process (see figure). MicroDEN leverages the benefits of a polystyrene culture surface, similar to the manual method, to provide for removal of non-adherent cells. Up to 25 million DCs can be reproducibly generated per unit, an equivalent or greater yield than manual production.
Benchmark phenotyping along with allogeneic T-cell proliferation and syngeneic antigen-specific functional assays demonstrated no phenotypic or functional differences based on manufacturing methodology.1 The same conventional phenotypes also resulted using culture medium containing either FBS or human serum, and when using serum-free medium.
In fact, in an allogeneic functional assay with immature DCs co-cultured with allogeneic CD3+ T cells for five days, MicroDEN-generated DCs proved better than manually generated cells at inducing T-cell proliferation. Proliferation was analyzed using CellTraceTM Far Red.
The RUO system will quickly demonstrate its superior approach to generation of DCs in routinely performed workflows and assays. Applications for MicroDEN-generated DCs include tumor-infiltrating lymphocyte (TIL) workflows that require a screening step, typically performed with autologous, manually produced, monocyte-derived DCs, for selection of appropriate subtypes and validation of neoantigen-specific T-cell receptors (TCRs).
To illustrate another example, a reliable supply of DCs is also needed for mixed lymphocyte reactions (MLRs) and antibody dependent cellular cytotoxicity (ADCC) assays that are widely used in screening of biologic and small molecule drugs. Higher T-cell proliferation and production of relevant cytokines are screens for antitumor potential.
It is no longer necessary to invest months to train technicians to manufacture DCs and still receive inconsistent results that vary batch to batch. The innovative MicroDEN perfusion system eliminates 55% of the manual steps, and delivers reproducible results in less time while greatly reducing contamination risk. Now, Corning and Flaskworks have shown that there is indeed a better way to manufacture DCs.
OK, EBIX, INC
On January 7, 2016, Ebix, Inc. (the “Company”) announced that it has scheduled its Annual Meeting of Shareholders (the “Annual Meeting”) to be held at Embassy Suites Alpharetta, 5955 North Point Parkway, Alpharetta, GA 30022 , on April 29, 2016 at 9:00 a.m., Eastern Daylight time. The Annual Meeting date has been changed by more than 30 days from the anniversary of the Company’s prior annual meeting of shareholders, which was held on January 9, 2015. The Annual Meeting date was delayed by Management and the Company’s Board of Directors in order to provide sufficient time for the filing of the Company’s annual report on Form 10-K for the year ended December 31, 2015.
Tell me any other company that holds it's annual meeting 14+ months after the close of the fiscal year
Here’s a shocker: Cancer patients facing delays in getting ‘innovative’ drugs
29th January 2020 by Anna Smith
http://www.pharmatimes.com/news/cancer_patients_facing_delays_in_getting_innovative_drugs_1323668
A new analysis report has found that most innovative cancer drugs face delays in reaching patients.
Researchers at The Institute of Cancer Research have now discovered that cancer patients are waiting longer for innovative new cancer drugs than for more conventional treatments, which suggests that the most “exciting” new therapies have not been successfully fast tracked.
As such, the team uncovered that the higher the level of innovation of a cancer drug, the longer it was taking to pass through clinical trials, licensing and appraisal for availability on the NHS.
The most innovative cancer drugs took 3.2 years longer to go from the filing of the patent through to NHS patients than low-innovation treatments, the data published in Drug Discovery Today found, as between 2000 and the end of 2016, the most innovative new drugs took 14.3 years to progress from patenting through to availability on the NHS – compared with 13.5 years for medium-innovation drugs and 11.1 years for the least innovative treatments.
Apparently, much of the delay seemed to occur in the period from the start of a phase I trial through to EMA authorisation – which lasted an average of 8.9 years for the most innovative drugs compared with 8.7 years for medium-innovation drugs and 6.8 years for the least innovative.
The study details the “major progress being made against cancer, with the average number of drugs being licensed each year more than doubling over the last decade”, commented study leader professor Paul Workman, chief executive of the Institute of Cancer Research.
But, he continue to say "it also makes clear that our regulatory systems are not keeping pace with advances in the science. It is taking longer for new drug to reach patients and, alarmingly, the delays are longest for the most exciting, innovative treatments, with the greatest potential to transform the lives of patients.”
Thanks Truthfan. It’s certainly no secret “the powerful forces” (paraphrasing Les) Northwest Bio is up against. The Pharmaceutical/Health Products Industry spent $300M lobbying last year, nearly double the next closest industry! There’s a fantastic (but somewhat lengthy) article about the historical relationship between Big Parma and the FDA here:
Thick as Thieves? Big Pharma Wields its Power with the Help of Government Regulation †
Leslie E. Sekerka, Lauren Benishek
https://law.emory.edu/ecgar/content/volume-5/issue-2/essays/thieves-pharma-power-help-government-regulation.html
Some excerpts:
The pharmaceutical industry spends hundreds of millions of dollars annually to market its products. Direct-to-consumer prescription ads are the second-fastest growing ad category, competing with other top marketers stemming from automotive, fast food, insurance, and cable/wireless providers. 10, 11 Ad spending for television by pharmaceutical companies has more than doubled in the last four years, representing a 65% increase in this genre since 2012. It is currently the seventh largest ad category in the U.S., investing $6.4 billion in 2016. 12 Table 1 offers examples of top U.S. drug advertisement expenditures in 2016. 13 Yet, greater ad spending does not necessarily correlate with product effectiveness. One of the most advertised drugs in 2016, Jublia (a toe fungus treatment), 14 costs about $600 a bottle but is reported to work in fewer than 20% of users.
In 2016, 80 prescription drug advertisements were televised every hour, totaling 1,920 drug ads directed at American viewers per day. 16 Television networks—ABC, CBS, NBC—along with cable channels like CNN draw millions of dollars from pharmaceutical advertising, approximately 8% of their ad revenue. 17 Given U.S. viewers watch about five hours of television daily, 18 many citizens are likely to spend more time listening to pharmaceutical advertisements than talking with their physician (typically 15 minutes per visit, four times a year).
All this advertising can increase the cost of prescription drugs. 22 Ironically, these ads actually serve as tax deductions for pharmaceutical firms. 23 Legislation to eliminate this deduction is currently being debated in the U.S. Congress but powerful lobby groups backed by the industry are challenging these reforms with tenacious veracity. . .
Today, the pharmaceutical industry contributes heavily to the FDA’s annual budget. Back in 1992, the (PDUFA) passed, making it the law for pharmaceutical companies to pay the FDA to review their applications for drug approvals. In response to a lethargic and burdensome process, this law was supposed to enable the FDA to work more efficiently and effectively, having more resources to conduct rigorous and timely reviews. In return, pharmaceutical firms would be able to send their products through the regulatory pipeline faster, and patients would receive new and potentially life-saving drugs more quickly. While the intent seemed to serve the greater good, many argued that PDUFA put the FDA into the pockets of the drug industry. 59 Avalere Health explored and reported how much pharma companies have actually paid the FDA through PDFUA, adding up the collected for different types of applications (e.g., for each prescription drug application with clinical data, the fee in 2016 was over $2 million). This report found that since PDUFA was passed in 1992, pharma companies have contributed $7.67 billion to the federal agency’s coffers. 60 This creates a interconnectedness between the two entities: a marriage between Big Pharma and the government can potentially blur the intent of government regulation and the role that it plays in protecting citizens.
Although interest groups have emerged to represent the rights of companies and patients alike (e.g., pharmaceutical manufacturers, governmental regulatory authorities, patent officers, academic and clinical researchers, attorneys, and political action committees [PACs]). With huge profits and a thousand paid lobbyists, Big Pharma often gains leverage in how legislation is crafted and/or abandoned. From 1998 to 2014, Big Pharma spent nearly $3 billion on lobbying, drowning out the voices of consumers and the interest groups that try to represent them. 61 While some stakeholder-driven activist groups, like Patients for Affordable Drugs, work to represent the voice of constituents, a number of powerful groups that claim to represent patient advocacy are tainted by special interest biases. One study shows that nearly all patient advocacy groups are manipulated or captured by the drug industry; over 80% of these groups take money from Big Pharma.
The (POGO) reports that at least 39 of 42 patient advocacy groups who participated in discussions with the FDA over agency review processes for prescription drugs received funding from pharmaceutical companies. 63 Additionally, at least 15 advocacy groups have representatives of drug or biotechnology companies on their governing boards. Congress recently passed the 21st Century Cures Act in 2016, authorizing $6.3 billion 64 in federal funding and weakening the FDA’s approval process. 65 worked on the bill, which served as a major financial boon to the drug and medical device industries. While patient advocacy groups were engaged, many were not independent. For example, the , a group that calls itself The United Patient Voice, has advocated before the FDA for faster drug approvals. Members of its board of directors include leaders from two of the main trade groups for the drug industry—Pharmaceutical Research and Manufacturers of America (PhRMA), and Biotechnology Innovation Organization (BIO)—along with executives from drug companies Sanofi, Johnson & Johnson, and Alkermes. PhRMA gave the National Health Council in 2014; in all, 77% of its funding came from the pharmaceutical and biotech industries, according to POGO. 66 The United Patient Voice Policy Action Team also has a PhMRA representative on it, along with an employee of Johnson & Johnson. . .
Big Pharma presents a disturbing ironic reality: the industry offers life-saving health benefits, and yet remains one of the least trusted. The reality is that “some of the largest drug companies in the world—the one’s that we rely on for life saving treatments—are convicted criminals.” 123 Are regulators enablers? Or, perhaps worse still, are they complicit in questionable or ethically unsound activities as a result of being driven by self-serving motives? Working to untie and address this Gordian knot of interrelated profiteering and motivated special interests will require increased stakeholder engagement and government activism. U.S. Senator Bernie Sanders (I-VT) asserts that “people must be prepared to stand up to powerful special interests like the pharmaceutical industry and like Wall Street.” 124 Before taking office, President Donald Trump said the pharmaceutical industry was “getting away with murder,” and vowed to do something about it. 125 The reality to date, however, is that Big Pharma has the power to continue to dictate the pricing of drugs in the U.S., where our legal platform continues to offer incentives for firms to extract exorbitant prices. Traditional common law remedies have not resulted in deterrence.
Excellent and thoughtful post senti, and I hope it will encourage at least a few prolific writers here to comment. It might not carry the weight of those industry groups, (or other large companies) but maybe if enough individuals do, it might have an impact. Interesting that there weren't more responses to your post, but it certainly deserves elevation.
Thanks for the post Umibe, I appreciate your effort to share, even if others don’t. It sounds like there was confirmation that they may be in control of the timeline like we suspected. It also doesn’t sound to me like they are in Merck’s pocket like others suspect, or maybe it’s just Les’ paranoia. Sometimes I feel like we are like “the blind men and the elephant” https://allpoetry.com/The-Blind-Man-And-The-Elephant I know there is a well thought out plan here. Every piece helps, but I’m anxious to get the whole picture. So many unknowns with this trial and company!
I guess Bob Apple got a little heat for their silence while the stock price got pushed below $4, but really? Revenue guidance range of $135 to $155 Million, after announcing that full-year 2019 revenue is expected to be at the upper end or exceeding revenue guidance of $115 to $120 million? They only estimate ~15% - 25% growth this year? I’m all for under-promising and over-delivering, but c’mon man, that is more like the worst-case scenario of Makena immediately taken off the market, zero revenue from Gx Forteo, and low growth of Xyo and Epi. I haven’t updated my model since Q3, but I’ve got $122M for 2019, and $170 for this year, and I thought that was being conservative.
senti, ex is just being ex. The company is APAC Biotech, and the “product” is an autologous monocyte-derived mature dendritic cell therapy called APCEDEN® that was approved based on the single-arm, phase II, ATTEST trial in India, and only approved in India because it wouldn’t pass the rigors of approval anywhere else. The results were published in the Journal of Cytotherapy in 2014. https://www.celltherapyjournal.org/article/S1465-3249(13)00786-X/pdf
Here’s an excerpt:
A total of 51 patients were enrolled for study and qualified as an intention-to-treat population. Thirteen patients died before they could receive the first dose, hence, 38 patients who received at least one dose were evaluated for safety and response. A total of 12 patients completed the study, which included six doses of DC immunotherapy and two post-treatment follow-ups in the course of 12 weeks.
Each sex had equal representation. Median age was 53 years. Most cases had multiple chemotherapy failure and metastatic disease. Most patients enrolled had cancer of the ovary, followed by colon and head and neck cancer. On-going co-morbid conditions such as hypertension, diabetes, chronic obstructive pulmonary disease and coronary artery disease were controlled with medication. A total of 14 different types of solid cancer were studied (Figure 4).
To analyze comparative data, the patients were divided into three cohorts. Cohort I included patients with progressive disease (PD), cohort II included patients with objective response (OR) and cohort III included non-evaluable patients; these were early dropouts and did not undergo response evaluation. Progression-free survival and overall survival were calculated from the date of enrollment and date of first infusion, respectively.
Baseline characteristics, source of antigen and instrument response of patients with OR are summarized in Table I. The cutoff date for analysis of data was December 5, 2012.
Safety and tolerability
Of 51 patients enrolled, 38 cases were evaluated for safety and efficacy, because 13 subjects died before the first dose could be given. Patients receiving at least one dose were evaluated for safety and response evaluation. In all, 225 infusions were administered and all were well tolerated, barring only one incident of chills and rigors associated with mild pyrexia reported during a single infusion. The patient continued on the study; symptoms were resolved and did not reappear during subsequent infusions. According to investigators, this could have been “possibly related” to study therapy.
vator
The other Merck DCVAX trial was supposed to be in Mainz Germany. Colorectal Cancer. It would be nice to know what has happened with that one.
senti, I’m quite sure that you’re right on this too. :) You’ve been keeping better track and for much longer than I have. But I think we’re talking about different warrants. LP’s D-2 warrants with a 5-year expiration date that I listed were issued in conjunction with her loans to the company (March & April 2018) right after the Regulation D Series B Preferred Stock Offerings to accredited investors (Dec 2017 & Jan & Mar 2018) who received D-2 warrants with a 2-year expiration date. (which is why it irked me a little) I guess since it was a loan and different from the preferred-share offer, that justified the longer expiration date. I don’t believe that these D-2 warrants had the exercise period shortened. From the 10-K April 2019:
LOAN AGREEMENT and PROMISSORY NOTE
March 14, 2018
5.2 Warrants. The Initial Warrants will be exercisable for a number of shares of the Maker’s Common Stock that is equal to fifty percent (50%) of the number of shares into which the full Repayment Amount would be convertible at a price of Twenty-three Cents ($0.23) per share. As provided in Section 1, the Initial Warrants become due and payable upon the Holder entering into the Loan. In the event that the Holder elects to convert all or any part of the Repayment Amount into Series B Preferred Stock (or Common Stock) of the Maker, the Conversion Warrants will become due and payable on a proportionate basis, up to a number of shares of the Maker’s common stock that is equal to fifty percent (50%) of the number of shares into which the full Repayment Amount would be convertible at a price of Twenty-three Cents ($0.23) per share. Both the Initial Warrants and the Conversion Warrants will only become exercisable upon the earlier of Common Stock bring available for issuance or June 1, 2018. Both the Initial Warrants and the Conversion Warrants will be exercisable at a price of Thirty Cents ($0.30) per share of Common Stock, will include cashless exercise, and will have an exercise period of five (5) years from the dates the warrants become exercisable.
Sent, it’s true that Linda Powers has about 9.5 million of the Series B, D-2 Warrants, but HER warrants don’t expire until May 2, 2023. It’s a minor point of contention with me.
Convertible Notes Issued for Loans Made By Chief Executive Officer
On March 14, 2018, Northwest Biotherapeutics, Inc. (the “Company”) and its Chief Executive Officer, Linda F. Powers, entered into a note and loan agreement for a loan of $4.0 million by Ms. Powers to the Company. The Note is convertible into Series B Preferred Stock at $2.30 for one share of Series B Preferred Stock and ten Class D-2 Warrants (the “Note”), with the Class D-2 Warrants on 50% of the principal due and issuable when the loan was provided, and Class D-2 Warrants on the other 50% of the principal and on all of the accrued interest due on a proportional basis in the event of conversion of some or all of the Note. Accordingly, the Company is issuing 8,695,652 Class D-2 Warrants to Ms. Powers now. The Note bears interest at a rate of 10% per annum, and is repayable upon 15 days' notice from the holder (and no later than five years from the date of the Note). Each share of Series B Preferred Stock is convertible into 10 shares of common stock when shares of common stock are authorized and available. The Class D-2 Warrants are not currently exercisable, will expire five years after they become exercisable and have an exercise price of $0.30.
On March 19, 2018, the Company and Ms. Powers entered into an additional note and loan agreement for an additional loan of $400,000 by Ms. Powers to the Company. This additional note is convertible into Series B Preferred Stock and Class D-2 Warrants on the same terms as the Note issued on March 14, 2018.
https://sec.report/Document/0001144204-18-015925/
March 2, 2020.
I believe Delaware law generally requires the annual shareholder meeting to be held within 13 months of the last one. If not, the Court of Chancery may order a meeting to be held upon the application of any stockholder or director.
survivor2012, it appears to be DCVax. I can’t remember who to give the credit to for first posting this, but Phase One provided a grant to UCLA for the trial.
https://www.phaseonefoundation.org/latest-news/cancer-researchers-develop-immunebased-therapies-for-deadly-brain-tumors
September 16, 2019
Researchers from the UCLA Brain Tumor Center received a $400,000 grant from the PHASE ONE Foundation to support their research in developing immunotherapies for glioblastoma, an aggressive and fast-growing type of brain tumor.
The grant, which is led by Dr. Linda Liau, chair of the neurosurgery department at the David Geffen School of Medicine at UCLA, and Dr. Timothy Cloughesy, a professor of neuro-oncology at the Geffen School of Medicine, helps fill an urgent need for novel and innovative approaches to better treat people diagnosed with the disease.
The average lifespan for someone with glioblastoma is often measured in months and less than 5% of people with glioblastoma live longer than five years. There are limited treatment options and there is a high probability that the tumor will come back after initial treatment. Currently, there is no standard therapy for recurrent glioblastoma.
“We are extremely grateful to receive this grant from PHASE ONE,” said Liau, who is also a scientist at UCLA’s Jonsson Comprehensive Cancer Center. “With this support, we have the potential to change the way glioblastoma is treated and provide patients with a new therapy that has the potential to support long-term survival.”
The funding will help open a clinical trial testing a combination treatment strategy using checkpoint inhibitors in conjunction with a personalized dendritic cell vaccine, which was developed by Liau at UCLA. The team hopes by combining the two treatments they will be able to create a new way to treat people with brain cancer, as well as develop new ways to track the immune response.
“We already have had preliminary success using checkpoint inhibitors to treat patients in a previous clinical trial,” said Cloughesy, who is also a scientist at the Jonsson Cancer Center. “By combining the two immune-based treatments, we hope to bring in more T-cells that will attack cancer cells that would otherwise go unnoticed by the body’s immune system.”
“Dr. Liau led the trial that gave my late husband seven healthy years, post terminal brain cancer diagnosis. At the time, she was a pioneer in the immunology approach to treatment, and I have watched her research progress to be even more effective and collaborative. She is a uniquely brilliant, compassionate and forward-thinking doctor and researcher, and I am incredibly pleased that PHASE ONE is able to help fund her next wave of research. Brain cancer is such a fierce and fickle disease, that requires aggressive, nimble and competent treatment – and her approach encompasses all of these qualities. I’ve witnessed her first group of patients from trials in the early 2000s exceed life expectancy and continue to thrive, which is proof that this is working, and that her efforts using a layered approach to finding a cure should be continued,” said Meritt Elliott, Board Member of PHASE ONE and co-founder of THE GREAT.
The UCLA Keytruda combo trial is recruiting . . .
https://clinicaltrials.gov/ct2/show/NCT04201873?term=NCT04201873&draw=2&rank=1
Recruitment Status : Recruiting
First Posted : December 17, 2019
Last Update Posted : January 16, 2020
Actual Study Start Date : January 8, 2020
Sorry if I’m late to the party.
Meanwhile, the regulatory bodies are beginning to collaborate . . .
FDA takes second action under international collaboration, approves new treatment option for patients with chronic lymphocytic leukemia
November 21, 2019
https://www.fda.gov/news-events/press-announcements/fda-takes-second-action-under-international-collaboration-approves-new-treatment-option-patients
Today, as part of Project Orbis, a collaboration with the Australian Therapeutic Goods Administration (TGA) and Health Canada, the U.S. Food and Drug Administration granted supplemental approval to Calquence (acalabrutinib) for the treatment of adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). This new approved indication for Calquence provides a new treatment option for patients with CLL or SLL as an initial or subsequent therapy.
“Today, as part of a U.S., Australian and Canadian collaboration known as Project Orbis, the U.S. approved a new treatment option for those living with chronic lymphocytic leukemia or small lymphocytic lymphoma. The FDA’s Project Orbis provides a framework for concurrent submission and review of oncology drug applications among the FDA’s international partners,” said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research. “We are pleased to continue working alongside our Australian and Canadian colleagues to facilitate new treatment options for patients and the FDA looks forward to working with other countries in future application reviews.” . . .
In addition to the international collaboration with Australia and Canada, this review used the Real-Time Oncology Review (RTOR) pilot program, which can streamline the submission of data prior to the completion and submission of the entire clinical application. RTOR, and its accompanying Assessment Aid, facilitated discussions among the regulatory agencies. These applications were approved four months prior to the FDA goal date. The FDA granted this application Priority Review and Breakthrough Therapy designation. The FDA granted approval of Calquence to AstraZeneca.
Project Orbis
https://www.fda.gov/about-fda/oncology-center-excellence/project-orbis
Project Orbis, an initiative of the FDA Oncology Center of Excellence (OCE), provides a framework for concurrent submission and review of oncology products among international partners.
Collaboration among international regulators may allow patients with cancer to receive earlier access to products in other countries where there may be significant delays in regulatory submissions, regardless of whether the product has received FDA approval. Pivotal clinical trials in oncology are commonly conducted internationally and these global trials are increasingly important for investigating the safety and effectiveness of cancer drugs for approval in the United States. Future drug development may benefit by establishing a greater uniformity of new global standards of treatment, leading to the optimal design of these important trials.
In 2004, FDA’s Office of Hematology and Oncology Products (OHOP) began holding regular teleconferences under a confidentiality agreement with other regulatory agencies to allow for exchange of information and collaboration on specific topics related to applications under review. Currently, OHOP holds a monthly teleconference with Australia’s Therapeutic Goods Administration, Health Canada, the European Medicines Agency, Japan’s Pharmaceuticals and Medical Devices Agency, and Switzerland’s Swissmedic. In addition, FDA and China’s National Medical Products Administration have initiated a quarterly meeting to discuss non-product specific regulatory issues facing worldwide drug development.
The first Project Orbis action took place on September 17, 2019, in conjunction with the Australian Therapeutic Goods Administration and Health Canada.
Project Orbis FAQs
Q: Which countries were involved in the first Project Orbis collaborative review?
A: The U.S. Food and Drug Administration (FDA), the Australian Therapeutic Goods Administration (TGA) and Health Canada (HC) took part in this application review.
Q: Will other countries be involved in future Project Orbis reviews?
A: Other countries may be involved in future application reviews.
Q: For the first Project Orbis review, what was the role of each country in the review process?
A: The three regulatory agencies collaboratively reviewed this application, allowing for simultaneous decisions in all three countries. The aim of this collaborative review was to identify any regulatory divergence across the review teams.
Q: Did the three countries issue the same drug labels for the two products involved?
A: No. Each country has its own format for the drug label. The regulators exchanged drug labels to learn about any potential differences. Only minor differences were noted. In Canada, the approved indication was slightly different than the approved indication in the United States and Australia.
Q: This was an FDA accelerated approval. Do Canada and Australia use similar expedited approval programs?
A: Health Canada used its conditional approval with conditions. TGA used its provisional approval with conditions of registration.
Q: Will Project Orbis be used only for supplemental oncology approvals (new indications for previously approved therapies) or will it be extended to New Drug Applications or original Biologics License Applications?
A: FDA and the other agencies will discuss the possibility of collaborating on NDA or BLA reviews for oncology products, but the process may be more complex due to proprietary information involved.
Cheers longfellow. Just curious if anyone heard any scuttlebutt (rumors or gossip) about it. I just saw an Environment Agency statement that required remediation steps, but I also read a while ago that the U.S. was pressuring the UK to block Huawei from its 5G network and wondered if that had anything to do with it.
http://plan.scambs.gov.uk/swiftlg/MediaTemp/1157139-897470.pdf
Well DONE, Hbpainter. That really takes the biscuit. I recall Bidwells stating that the 17 acres had “significant residential possibilities.”
1,072,622,133
From the prospectus dated 01/03/2020:
Shares of Common Stock Outstanding After Offering: 618,455,638
Shares of Common Stock subject to outstanding options: 101,658,932
Shares of Common Stock reserved for issuance upon exercise of outstanding warrants: 352,507,563
longfellow, I didn’t have time to post but I also have interest in Cobra Bio. As Doclogic said, Cobra Bio certainly has direct relevance to Northwest Bio.
"This acquisition is central to Cognate's strategy to build on its existing offerings and create an enterprise platform for life cycle management of cell and gene therapy products, accelerating the availability of new technologies to patients that need them most," J. Kelly Ganjei, Cognate’s CEO, said in a release. "Cobra is a well-established leader in the development and manufacture of a variety of DNA and viral vectors that our current and prospective clients urgently need. “The combined Cognate-Cobra expertise, infrastructure, and geographical footprint immediately positions both businesses to better respond to current and future market needs more quickly, effectively, and comprehensively,” Ganjei continued.
Proposals For The Former Spicers Site
https://www.theformerspicerssite.co.uk/proposals/Former-Spicers-Site-proposal-APR2019.pdf
I’m not sure if this has been posted, but I hadn’t seen it before. It appears that Huawei withdrew their planning application in September. I haven’t read through the plans and docs,of the planning application, but it looks like maybe there was some environmental concerns about potential water contamination but I’m not sure. Has anyone heard what’s going on now?
http://plan.scambs.gov.uk/swiftlg/MediaTemp/1157139-916704.pdf
I was actually looking for an application for change of use / rezoning for the 17 acres Northwest Bio retained. Has anyone been keeping up with the planning applications and know if this has been accomplished? I would think that if they were unable to get the change of use, they might qualify for a rural exception due to the shortage of affordable housing?
Potential rural exception sites
https://www.scambs.gov.uk/housing/housing-development/potential-rural-exception-sites/#/content/content/edit/4123
Yes it has been posted but thanks for the reminder. And yes, both companies are sponsors and will have booths at the event, but are not scheduled to speak. There are some interesting topics though.
Phacilitate Leaders World & World Stem Cell Summit 2020
JANUARY 21-24, 2020 HYATT REGENCY, MIAMI
Northwest Biotherapeutics
Booth number: S52
https://www.phacilitate-leaders-world.com/agenda
Thanks for the post longfellow
Well what does 'Operationally Practical for Commercialization' actually mean?
Cell and gene therapy GMP manufacturing in the UK
Capability and capacity analysis November 2018
https://ct.catapult.org.uk/sites/default/files/publication/2018%20GMP%20Manufacturing%20Report_FINAL.pdf
FYI - Advent is on page 19
Not sure if this has been posted, but wanted to show the many ways that clean rooms can be configured. I’ve been waiting to see the 2019 report for an update on Advent but there are no pics :(
Cell and gene therapy GMP manufacturing in the UK
Capability and capacity analysis November 2019
https://ct.catapult.org.uk/sites/default/files/publication/2019%20GMP%20Manufacturing%20Report_v6_0.pdf
ex, I think you are correct that Linda has said that the process is about 7 or 8 days. From what I understand, for autologous therapy manufacture, each patient’s own cells constitute one batch, and if the process is open, then manufacturing requires dedicated equipment and separate cleanroom processing suites to separate each patient-specific product. Each batch must be segregated to prevent cross contamination, and a high-grade cleanroom is required, typically grade B. I think Linda has talked about this slow, manual process and “men in space suits” that was used for the trial. I doubt very seriously this method will be used for commercial production however. Implementing isolators dedicated to one product or patient and/or using automated closed systems alongside single-use fluid paths would allow the processes to be fully enclosed. That approach reduces surrounding cleanroom classification to grade C. Several vendors provide fully automated and closed systems suitable for cell therapy applications. Two of these companies are Terumo BCT and FloDesign Sonics, who signed collaboration agreements with Cognate last fall.
Nice post iwasadiver. Thanks!
mani, has it occurred to you that the investors who participated in the financing last week were not small minded, short-term investors who were looking to scalp a penny or two, but were instead long-term supporters of the company who were interested in continuing to fund the company to see a much larger payoff down the road, as well as extending their warrants that might otherwise expire?
The company cannot and does not give reassurances, and if you had read the prospectus, you would know that investors are actually warned of the “high degree of risks” involved in the investment. And I would add that if the 12.5 million shares were bought on the open market, it would not have the dilutive affect that may have caused the decline, and the buying pressure of that many shares would instead likely increase the share price in the short term.