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Actually Titan there is a difference, Refractory refers more to the stubborn tumors that although they have a low TIL environment are still resistant to a treatment regimen due to other factors.
My understanding is it's the same trial. Anytime there is talk about a metastastic melanoma combination study, They can be referred to as a phase 2 or phase 2B clinical trial. Phase IIA is specifically designed to assess dosing requirements (how much drug should be given). Phase IIB is specifically designed to study efficacy (how well the drug works at the prescribed dose. I do think that they have been working with both aspects during this phase 2 trail.
Well you're either wishing me a midday greeting or you are telling me about what the fourth studio album by British grime artist Skepta is.
Dr. Pierce calls the staining of T cells in the tumor a, "sticky wicket" as far as the FDA is concerned. I think this foreshadowing a problem with a registration trial with a combination stain being used with PD – 1, like what is being used in our P2b.
"Changing the Nature of the Game"
Sitting Down With… Robert Pierce, Chief Scientific Officer, OncoSec, San Diego, CA, USA
What motivated your career in pathology?
I knew all along that I wanted to do mechanistic medical research. I was sitting in medical school, thinking, “Okay, what’s my quickest route back into the lab?” so I asked my mentors, who were doing lab-based work and patient care, “How can I do that?” They said, “Don’t. Go into pathology.”
Although choosing pathology meant I gave up seeing patients, I never gave up interacting – I see the doctors and their patients as “my patients”, which I find just as rewarding.
Because the Air Force paid for my medical school, I had to give them time back after I finished my residency – and, in retrospect, that was a phenomenally good thing. The people I saw starting out as junior faculty had to simultaneously get up to speed as clinicians and start building a lab. I don’t know how they did it; both of those things are overwhelming. But in the Air Force, I was in a really good clinical setting that let me come up to speed as a practicing diagnostician – so by the time I started my first academic job at the University of Rochester, my clinical chops were fine and I could really focus on building my lab.
I arrived at the University of Rochester fairly pluripotent as a pathologist; I could have developed in a number of different ways. I wanted to join a group that I could learn a lot from, so I re-tooled and became an immunologist. Immunologists and pathologists speak different languages, and by virtue of having a foot in each world, I was able to translate things better. It set me on the path of understanding what I call immune subversion – that is, how tumors block the immune system.
Why the move to pharma?
When I was writing my first R01 grant, I got some critiques that forced me to build a drug for the very first time. It was a polymeric drug delivery vehicle to get my molecule to my target cells, so I started working with a friend in biomaterials, and at that point, I got the bug. I think that was probably the seed of the demise of my academic lifespan, because then I wanted to take what I was discovering and apply it to actually making a drug.
Personal reasons took me to the Bay Area and, out of the blue, a fantastic job emerged at DNAX, which is legendary in immunology. In my mind, the place was a scientific utopia. Schering-Plough, amazingly, funded this research institute and never really put much pressure on the drug development aspect – so for almost 20 years, it produced great science. It’s formed so much of what we know in immunology today. And when they decided to transform DNAX into a drug discovery enterprise, they brought in Dr. John Curnutte from Genentech, who was a real proponent of translational medicine. He felt they needed pathology to really understand the biology and mechanisms of disease at the level of tissue architecture and cellular organization. I took the job in a heartbeat and I’ve been happier than a pig in slop ever since.
What was the story of PD-1?
When I was at DNAX (then Schering-Plough Biopharma), the PD-1 program came to us through the acquisition of Organon. My understanding was that Organon was preparing to move forward in development (i.e., humanization of the monoclonal antibody and Investigational New Drug application) without a “companion” mouse antibody and mouse-based IND enabling studies. This was a pretty bold, forward-thinking approach. Although it was clear from the literature that anti-PD-1 was a strong candidate molecule for immuno-oncology, Schering-Plough took a more conservative approach and we were tasked with building the mouse surrogate program. The immunohistochemistry antibody we developed is still moving forward as a companion diagnostic at Merck; it’s a brilliant antibody, one of the best out there. But when Merck and Schering-Plough merged in 2009, the PD-1 program was deprioritized, at least until Bristol-Myers Squibb published Phase I data with their candidate. Then it was like Lazarus – raised from the dead! It’s amazing that Merck still got the first approval in the US. I think they benefited from going after refractory melanoma patients as their main indication; that triggered the breakthrough therapy designation.
It’s exciting that we have such a good idea who responds to anti-PD-1 and who doesn’t. That’s critical to why PD-1 development is going so fast – in large part, we understand the mechanism of action, so we can come up with a rational understanding of how to use it and what to pair it with in combination therapy.
My first a-ha moment came when I saw tumors IHC-stained with PD-1 and PD-L1. Patients who respond to anti-PD-1 have cytotoxic T cells in their tumors, and you only need immunology 101 to say, “Wow! The T cell coming in is generating a cytokine,” which upregulates PD-L1 to shut off the T cells. It’s a homeostatic mechanism we evolved to avoid excessive immune reactions. Every reaction contains its own braking mechanism and tumors hijack these brakes to the immune system.
It took a long time to convince the scientific and medical community that immunotherapy would work. In fact, it’s been more than 100 years of chasing Dr. Coley’s vision of harnessing immune responses to treat tumors. If you think about where we are with anti-PD-1 and other immunotherapies today, where might we be if this transformation had happened earlier? Where would patients and industry be if that were the case?
What new treatment strategies hold most potential?
The future is in combination immunotherapies – I predict they’ll become the backbone in many indications. We just need to figure out how to use current targeted agents and chemotherapies judiciously.
I think the most important question that we need to answer in immuno-oncology now is: how do you make PD-1 non-responders into responders? That’s our current strategy at OncoSec – and our primary candidate is intratumoral delivery of IL-12. As a cytokine, it’s a chief driver of anti-tumoral immunity; it turns on all the mechanisms of antigen presentation and processing that tumors try to suppress, so it’s a good choice for targeting PD-1 non-responders and we’re seeing very good systemic anti-tumor response effects in the clinic so far.
Immunotherapies in general are not innocuous. PD-1’s safety profile is pretty good, but when we combine therapies, we’re going to have to be sensitive to synergistic immunotoxicity. That’s a benefit of moving toward a multimodal therapeutic paradigm, including intratumoral therapy – we can harness the treatment efficacy without the systemic exposure and toxicity. IL-12, for instance, used to be given as a recombinant protein drug; it was efficacious, but quite toxic, which is why it wasn’t pursued further. Giving it intratumorally, we don’t see any IL-12 in circulation, so we aren’t seeing the systemic toxic effects that we know systemic IL-12 administration would produce.
Some of the real luminaries in the literature today are beginning to talk about intratumoral therapy. I think we’ll see these therapies come of age in the next decade; Amgen’s T-VEC, a virus that encodes GM-CSF, has met with some success, but there are a lot of different ways you can approach it and I think others will follow suit.
I also think we’ll come back to DNA damage and repair. Tumors are dependent on their ability to mutate; they have to, because that’s how they defeat the immune system and the chemotherapies we throw at them. But this can be their Achilles heel; they become dependent on DNA checkpoints, unlike normal cells, so we have a therapeutic leverage point. I think we’ll see a resurgence of this as a field to explore.
I think one of the benefits of immunotherapy is that you’re not going directly after the tumor, but instead you’re educating the immune system.
How do you see the role of pathologists evolving?
It’s going to be increasingly important for pathologists to perform and interpret companion diagnostic tests in clinical labs. But that gets into a really sticky wicket about companion diagnostics – the FDA guidance seems very arbitrary. For instance, we might use immunohistochemical stains to diagnose melanoma, but then if we want to use the PD-1 or PD-L1 stain as a companion diagnostic for a PD-1 drug, suddenly it has to go through FDA approvals. I know the FDA’s mandate is to protect the public health, and they obviously want to alleviate the risks associated with an unregulated test. Unfortunately, their process was set out to make drug development more expeditious and cost-effective, but in fact, it makes costs higher and takes more time. I think there are cases where it stands in the way of being innovative.
On the research side, it’s clear that we can’t just grind up tumors irrespective of what cells are in there and get an answer. We need to understand what interactions are occurring within the tumor. And those are the sorts of insights that come out of a sensitivity to tissue architecture and cell function; that’s why we need pathologists to further our understanding of tumor behavior, discovering potential mechanisms and research angles. That’s where I’ve spent my entire career. The technology is coming, but you still need the brain behind the scope.
I think we really are at this transformative moment in oncology. We’re no longer just trying to out-poison the tumor; we’re changing the nature of the game, and I’m amazed that the message hasn’t gotten out. People just don’t know that we’re doing that. I think everyone should be as excited as I am – it’s a brilliant time to be in this field!
Yeah Titan, there's no way the price is going to drop below $1.60, so I thought I might as well get in here. This really isn't gonna go anywhere until that phase 2B comes out and then the other supportive news items that trickle in as well. And good luck to you as well my friend. From here it is simply onward and upward!
Hi TJ, I've been adding the last couple of days I only had a couple of 100 share fills– – the rest were midday at 3 to 4000 shares, with the 10,000 share amounts being filled within 20 minutes of close of market.
My fellow Longs, don't want to be sitting on the sidelines now. Just picked up another 5100 shares for myself and invested another 14,600 Shares for my elderly parents. The 10,917 shares in the last 30 minutes was the last of my purchases. I've been here since 2012 with a goal a buy-and-hold and wait out for a buyout. I'm not much for small talk anymore it all seems like Smalltalk until we get that exit opportunity and the true valuation of this company. In case you don't recognize it that last thought is Punit Dhillons.
May I encourage the Ignore button
OncoSec Appoints Sharron Gargosky, PhD, to Chief Clinical and Regulatory Officer
OncoSec Medical Incorporated (NASDAQ: ONCS), a company developing DNA-based intratumoral cancer immunotherapies, today announced Sharron Gargosky, PhD, has been appointed to Chief Clinical and Regulatory Officer, effective as of September 1, 2016. Dr. Gargosky previously served as OncoSec's Head of Clinical Development and Operations, as a consultant, since February 2016. She now joins OncoSec's management team to oversee the progress of innovative clinical research studies through all phases and to help define OncoSec's overall clinical business strategy.
"Dr. Gargosky continues to be an effective and powerful force in advancing our clinical programs towards commercialization," said Punit Dhillon, President and CEO of OncoSec. "Her keen understanding and strategic background in clinical operations and overall program development will significantly advance our melanoma development program and registration pathway for ImmunoPulse® IL-12 in combination with anti-PD-1 in patients with advanced melanoma. Dr. Gargosky will also help progress OncoSec's overall development efforts to more broadly address anti-PD-1 resistant cancers. We're thrilled to have her on board and contribute to the strength of OncoSec's leadership team."
Dr. Gargosky has over 20 years of experience in clinical development and operations in the field of pharmaceutical and biologic development having managed global programs from early research phase through the U.S. Food & Drug Administration (FDA) approval process. Prior to joining OncoSec, Dr. Gargosky was the Chief Technical and Operations Officer at Prima Biomed, Ltd., where she led the immuno-oncology program in ovarian and pancreatic cancer overseeing international manufacturing, regulatory approvals, and clinical execution. Prior to Prima Biomed, Dr. Gargosky served in positions of increasing clinical and scientific responsibility at biopharmaceutical companies including Pharmacia, Medicis, and Hyperion Therapeutics. In her career, she was involved in small molecule development attaining orphan drug approvals in rare diseases. Dr. Gargosky received her PhD from the University of Adelaide, Australia and completed her postdoctoral fellowship at Stanford University.
As an inducement to Dr. Gargosky entering into employment with OncoSec, the Compensation Committee of the Board of Directors of OncoSec approved the grant to Dr. Gargosky of an option to purchase up to 270,000 shares of OncoSec's common stock at an exercise price equal to the fair market value of the stock on the September 1, 2016 grant date. The option will have a term of ten (10) years and will generally be forfeited if not exercised before the expiration of that term, or, if earlier, after the ninetieth (90th) day after termination of Dr. Gargosky's employment. Twenty-five percent (25%) of the shares underlying the award vested on the grant date and the remaining seventy-five percent (75%) of the shares underlying the award shall vest in thirty-six (36) equal monthly installments thereafter. The option was granted outside of OncoSec's 2011 Stock Incentive Plan, but it is subject to terms similar to those of non-qualified stock options granted under such plan. This description of the inducement option grant to Dr. Gargosky is in satisfaction of the disclosure requirements set forth in NASDAQ Listing Rule 5635(c)(4).
About OncoSec Medical Incorporated
OncoSec is a biotechnology company developing DNA-based intratumoral immunotherapies with an investigational technology, ImmunoPulse®, for the treatment of cancer. ImmunoPulse® is designed to enhance the local delivery and uptake of DNA-based immune-targeting agents, such as IL-12. In Phase I and II clinical trials, ImmunoPulse® IL-12 has demonstrated a favorable safety profile and evidence of anti-tumor activity in the treatment of various solid tumors and has shown the potential to reach beyond the site of local treatment to initiate a systemic immune response. ImmunoPulse® IL-12, OncoSec's lead program, is currently in clinical development for several indications, including metastatic melanoma and triple-negative breast cancer. The program's current focus is on the significant unmet medical need in patients with melanoma who are refractory or non-responsive to anti-PD-1/PD-L1 therapies. In addition to ImmunoPulse® IL-12, the Company is also identifying and developing new immune-targeting agents for use with the ImmunoPulse® platform. For more information, please visit: www.oncosec.com
Cautionary Note Regarding Forward-Looking Statements
This press release contains "forward-looking statements" within the meaning of the U.S. Private Securities Litigation Reform Act of 1995. Forward-looking statements can be identified by words such "will," "strategy," and similar references to future periods.
Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on management's current preliminary expectations and are subject to risks and uncertainties, which may cause our results to differ materially and adversely from the statements contained herein. Potential risks and uncertainties that could cause actual results to differ from those predicted include, among others, the following: uncertainties inherent in pre-clinical studies and clinical trials, such as the ability to enroll patients in clinical trials and the risk of adverse events; unexpected new data, safety and technical issues; our ability to raise additional funding necessary to fund continued operations; and the other factors discussed in OncoSec's filings with the Securities and Exchange Commission.
Undue reliance should not be placed on forward-looking statements, which speak only as of the date they are made. OncoSec disclaims any obligation to update any forward-looking statements to reflect new information, events or circumstances after the date they are made, or to reflect the occurrence of unanticipated events.
Good morning Trading.Jeff, if I remember correctly about the construction of the trial, it is to assess and select only low till responders – – administer ImmunoPulse – – with systemic intravenous treatment of Keytruda. The test design is to clarify OncoSec's ImmunoPulse platforms ability to increase the TIL environment and then measure the overall response rate regarding the combination effect. In other words – – will the effect be equal to its individual parts, or will ImmunoPulse and Keytruda affected be greater than the sum of its parts.
Ridgeback Capital Investments adds OncoSec Medical Inc (ONCS) to its portfolio
By: Ryan Silvi|Last Updated: August 30, 2016
OncoSec Medical Inc (ONCS) : Ridgeback Capital Investments added new position in OncoSec Medical Inc during the most recent quarter end. The investment management firm now holds 1,292,614 shares of OncoSec Medical Inc which is valued at $2,249,148 , the company said in a statement filed on Aug 12, 2016 with the SEC.OncoSec Medical Inc makes up approximately 16.42% of Ridgeback Capital Investments’s portfolio.
Other Hedge Funds, Including , Renaissance Technologies boosted its stake in ONCS in the latest quarter, The investment management firm added 79,800 additional shares and now holds a total of 123,200 shares of OncoSec Medical Inc which is valued at $214,368.Vanguard Group Inc boosted its stake in ONCS in the latest quarter, The investment management firm added 13,025 additional shares and now holds a total of 430,031 shares of OncoSec Medical Inc which is valued at $748,254. Acrospire Investment Management added ONCS to its portfolio by purchasing 1,112 company shares during the most recent quarter which is valued at $2,124.
Waitforit! Indeed we shall, and for those of us who have stayed the coarse because we can see the potential of the science Will Be Rewarded in the short-term (relatively speaking) by years end -- and my hope is then a forth coming buyout at or above $4 billion.
This may seem optimistic, but if you calculate the worth of a platform that opens the door to non-responders in multiple cancer indications.
I like this part Titan:"These findings represent an advance in the field of cancer immunotherapy," said Adil Daud, MD, director of Melanoma Clinical Research at the UCSF Helen Diller Family Comprehensive Cancer Center. "Many tests examining PD-L1 levels in tumor tissue can only modestly discriminate between responders and non-responders. This analysis accurately predicts response to anti-PD-1 therapy and can be utilized in the clinic to appropriately select patients with a high likelihood of achieving a clinical response to PD-1 pathway inhibition."
Yep, that's it exactly hs
Bristol Swings For The Fences And Strikes Out
Aug. 8, 2016 12:33 PM ET
Since the first anti-PD-1 agents secured approvals the first-line lung cancer indication has represented the biggest prize on offer. Today Bristol-Myers Squibb (NYSE:BMY) paid the price for overreaching with Opdivo and trying to knock Merck & Co’s (NYSE:MRK) Keytruda, which had a slight time advantage, out of the park.
The failure of Bristol’s Checkmate-026 trial is a huge blow for the group, whose stock crashed 17% this morning – losing $20bn of market cap – while Merck climbed 7%. Bristol now awaits results of a Yervoy combo study in this setting, after what looks like immuno-oncology’s biggest upset so far.
It is very easy to say in hindsight, but the problem with Checkmate-026, an open-label trial testing Opdivo in 535 first-line NSCLC patients, was its design. Bristol had moved aggressively, recruiting relatively low PD-L1-expressing patients, and the first analysis concerned 5% or higher expressers, with the primary endpoint set at progression-free in preference to overall survival.
Perhaps it was just bad luck, or maybe Bristol had feared falling behind Keytruda. The Merck drug’s first-line NSCLC trial, Keynote-024, rendered a positive topline result in June, hitting both co-primary endpoints of PFS and OS – but in patients expressing PD-L1 at 50% or above.
Until today the battle was playing out exactly as the sellside had expected. Keytruda was to be first to yield positive first-line NSCLC data in a narrow patient population, before Opdivo regained the upper hand with a benefit in lower PD-L1 expressers.
Indeed, on its second-quarter conference call just a week ago, Bristol was still boasting how Checkmate-026 could allow it to broaden the patient population further: if >5% expressers yielded positive data the company could look at the effect in those with PD-L1 at >1%, representing 70% of first-line patients.
Moreover, a positive PFS benefit could be backed up by OS data, a secondary endpoint. “And we can still file without a positive OS result,” said Bristol’s chief scientific officer, Francis Cuss.
Now, with Bristol today saying Checkmate-026 was a bust, failing to show a PFS benefit in the 5% or greater PD-L1-expressing population, the rulebook has been torn up.
Early worries
Still, there had been worries among some analysts about an initial reliance on PFS. On Bristol’s fourth-quarter call Citi’s Andrew Baum specifically raised the issue of so-called “pseudoprogression” – a known problem with some previous immuno-oncology trials that had obscured a potential benefit by making it seem like active patients were progressing as fast as the control group.
But realistically Bristol probably had little choice but to go with PFS. Waiting for an OS benefit to mature would have been unrealistic in a first-line study with the breadth of Checkpoint-026.
As it is Bristol might now try to cut the patient population down, looking at only the 50% or higher expressers, but since this had not been specified in the design of Checkmate-026 it would be exploratory, and would hold little water as regards regulatory filings.
Most likely Opdivo will for now be restricted to second-line use, an approved indication, with first-line reserved for Keytruda in its biomarker subgroup. Checkmate-227, a complex first-line NSCLC trial involving several combinations as well as Opdivo monotherapy, is under way but does not read out until 2018.
As well as Merck making strong gains, AstraZeneca (NYSE:AZN) and Roche (OTCQX:RHHBY) shares spiked today, up 6% and 2% initially, though the UK group quickly faded (Therapy focus – First-line lung cancer is an Opdivo vs Keytruda showdown, June 10, 2016).
Until now EvaluatePharma’s consensus of sellside forecasts saw Bristol generating 60% of 2022 Opdivo sales in NSCLC, across all lines of therapy. Evercore ISI’s Mark Schoenebaum put the size of the first-line NSCLC market at over $12bn, and neatly summed up the Checkmate-026 failure, calling it “possibly the biggest clinical surprise of my career”.
The consensus-based NPV of Opdivo in all forecast uses amounted to a staggering $71bn, or 57% of Bristol’s market cap; little wonder that the sell-off was so extreme today.
In terms of market cap gains and losses there have been other immuno-oncology rollercoaster moments, including Opdivo snatching Keytruda’s early lead away from it, and Bristol reporting underwhelming and somewhat confusing biomarker data in a second-line NSCLC trial at last year’s Asco meeting; in hindsight perhaps this was the canary in the coalmine.
While much more work still needs to be done to elucidate the importance of various biomarkers, the Checkmate-026 disappointment has triggered a massive shift in sentiment.
This morning, Bristol-Myers says lung cancer drug (Opdivo)failed to meet primary endpoint--Merck (NYSE:MRK) +10.7% premarket on potentially reduced competition for its Keytruda lung cancer drug.
Some Charts with events
Jul 27, 2016 Triple Moving Average Crossover (4-day 9-day 18-day) Short-Term Bullish
Jul 25, 2016 Short-term KST Short-Term Bullish
Jul 22, 2016 MomentumW Short-Term Bullish
Jul 21, 2016 Momentum Short-Term Bullish
Jul 21, 2016 Price Crosses Moving Average (21-day) Short-Term Bullish
Jul 21, 2016 Commodity Channel Index Short-Term Bullish
Jul 18, 2016 MACD Short-Term Bullish
Jul 22, 2016 Intermediate-term KST Intermediate-Term Bearish
Jul 21, 2016 Price Crosses Moving Average (50-day) Intermediate-Term Bullish
Jun 03, 2016 Triple Moving Average Crossover (4-week 9-week 18-week)W Intermediate-Term Bearish
May 27, 2016 HammerW Intermediate-Term Bullish
I think your right TJ, and I gotta say, its nice to see him out there describing what Immunopulse can do. He has been off the grid for a while.
Fred Hutchinson Cancer Research Center:
Uncloaking the tumor: Can in-situ vaccination solve the problem of anti-PD-1 non-response?
Jul 26, 2016
3:00 pm - 4:00 pm
Thomas Building, Sze East/West
Robert Pierce, MD, Chief Scientific Officer, OncoSec Medical Inc.
Sponsor: Immunotherapy Integrated Research Center
Rodman & Renshaw Assumes OncoSec Medical at Buy, Announces $6.00 PT
Paul Quintaro , Benzinga Staff Writer
July 21, 2016 7:03am
In light of those articles Titan, my wife and I decided in the last 2 min. before the close to pick up @ 1.699 = 6017 shares -- now all in with 20,000 total. Now to Waitforit--the OncoSec P2b News.
Merck Cutting Drug Research Jobs at Three East-Coast Sites
Pharma giant plans new laboratories near Boston and San Francisco, increasing focus on microbiome research
By
Peter Loftus
Updated July 12, 2016 2:39 p.m. ET
Merck & Co. said it plans to lay off research-and-development workers at three East Coast sites in a shake-up of its early-stage drug-hunting efforts that also includes a new focus on the health effects of micro-organisms that populate the human body.
A Merck spokeswoman said the job cuts, and some employee transfers, would affect less than 10% of “discovery, preclinical and early development” employees in Kenilworth, N.J., Rahway, N.J., and North Wales, Pa. The company’s headquarters are in Kenilworth.
The move marks the latest round of layoffs and reorganization for Merck’s research unit, which was once known for cutting-edge drug development but which hit a fallow period late last decade.
Other large drugmakers including Pfizer Inc. and GlaxoSmithKline PLC also have cut R&D spending or reorganized research units in recent years to become more productive relative to their spending.
The Merck spokeswoman said the company is making the changes to allow it to have “earlier access to emerging external science and technology to augment our leading discovery and development capabilities.
At the same time, Merck plans to start new laboratories in Cambridge, Mass.—near Boston—and the San Francisco Bay Area, as part of a trend among large drug makers to try to tap into hot clusters of biotechnology start-up activity and academic research.
In Cambridge, Merck is creating a new “exploratory science” group that will focus on emerging research, including the role of the so-called microbiome in human health. The microbiome is the set of bacteria and other micro-organisms that reside in the human body. Emerging research suggests that finding ways to alter the microbiome can treat certain conditions, such as inflammatory bowel disease.
Merck’s head of infectious-disease discovery research, Daria Hazuda, will lead the Cambridge exploratory science site, the spokeswoman said. The new Cambridge labs are scheduled to open later this year.
Merck also plans to set up a research site in South San Francisco in early 2017 that initially will focus on cardiovascular, metabolic and cancer research.
The new changes are the latest at Merck since Roger Perlmutter took over as R&D chief in 2013 with a mandate to improve the once-storied division. That year, Merck embarked on a plan to reduce its total work force by about 20%, including cuts among R&D scientists, as the company narrowed its focus to certain treatment areas, such as cancer immunotherapy.
Dr. Perlmutter also boosted Merck’s scouting of external drug R&D projects that it could acquire or license.
Merck has reduced its annual R&D spending to $6.7 billion last year from $8.5 billion in 2011.
The pharmaceutical R&D blog “In the Pipeline” reported some of the Merck changes on Tuesday.
The Merck share price rose 0.6% to $59.71 in recent trading on Tuesday.
(Long-term buy and accumulate style, I plan on doubling down soon, prior to science readout. Looking for acquisition.)
2016-06-25 / Health & Fitness:
Sci-fi or silver bullet? How immunotherapy is revolutionizing cancer treatment
Like any promising treatment, immunotherapy needs more research, time and investment to achieve its full life-saving potential.
Could the kind of cancer treatment credited with saving former President Jimmy Carter soon work for everyone? News coverage of Carter's recovery and in-depth coverage by media giants like TIME Magazine and 60 Minutes could lead you to believe that immunotherapy will be the silver bullet that ends cancer for everyone. Like any promising treatment, immunotherapy needs more research, time and investment to achieve its full life-saving potential.
"New treatments that harness the body's immune system to fight disease are changing how we view cancer treatment," says Punit Dhillon, president and CEO of OncoSec Medical Incorporated, a company engaged in immunotherapy research. "And while immunotherapy has shown great promise in fighting cancer, cancers are unique to the individual and adaptable. Research has shown combination therapies may be even more effective in defeating cancer's ability to adapt and survive in the body."
How immunotherapy works
To understand how immunotherapy can work, it's important to know how cancer operates in the body. When cancer cells grow and spread, they develop the ability to evade the body's immune system. If the body does not recognize cancer cells as a threat, they may be safe from an immune system attack. Cancer cells also adapt and can become resistant to traditional cancer treatments over time. While traditional treatments may shrink or eliminate tumors, if any cancer cells remain after treatment, they could adapt and begin growing again.
Immunotherapy seeks to reverse this immune tolerance, to once again identify cancer cells as a threat and target them for elimination. A class of immunotherapies, called checkpoint inhibitors, have shown great promise by re-invigorating T-cells, which are the immune system's fighter cells, so they can again recognize and attack cancer cells. This approach worked for former President Carter's brain tumor treatment.
The benefits of immunotherapies are undeniable. Successful immunotherapy attacks only cancerous cells, leaving healthy tissue undamaged. Using the body's own defenses to fight cancer lacks some of the debilitating side effects associated with traditional treatments, such as chemotherapy and radiation. Immunotherapy can also train the immune system to remember cancer cells. This "memory" could remain effective long after treatment ends.
Another aspect of the challenge
"While checkpoint inhibitors can be very effective, many cancer patients don't have enough of a critical type of cell - called tumor-infiltrating lymphocytes (TILs) - for this type of therapy to be effective," Dhillon notes. "Researchers are finding that only the minority of patients, about 30 to 40 percent, respond when treated with just this type of therapy alone."
Scientists are looking to combine immunotherapies with other kinds of existing cancer treatments to realize the full potential immunotherapy has to offer.
OncoSec is currently developing a technology, ImmunoPulse, that aims to stimulate anti-tumor immune activity and drive essential TILs to the tumor area. The company is conducting research that shows this priming therapy will help increase patient response rates to checkpoint inhibitors by driving TILs. The aim is to develop a therapy that, when combined with other immunotherapies, will help the body's immune system operate even more effectively against cancer.
"To the public-at-large, immunotherapy is a relatively new concept that may seem like it borders on science fiction, but immuno-oncology researchers have made very real, positive progress," Dhillon says. "We've already learned we can leverage the body's own defenses to combat cancer. Now, our goal is to better understand how to make different therapies work better together so patients have safer and more effective treatment options."
"True valuation of a company is NEVER reflected UNTIL we get an exit opportunity" PD said.
I would like to also add the emphasis on exit opportunity versus licensing agreement.
Nice find Titan, this is my position as I wait for just that!
Presentation--Tue, Apr 19, 3:45 - 4:00 PM, their 15 minutes of fame.
Doesn't seem like a lot of time for a breakthrough talk--is that a typical amount of time for something this potentially impactful data Guys?
When I initially read this PR Lazers, back on Nov. 25, 2014, I took the "Supply" and "Provide" to mean the device/drugs were at the provider's and not the sponsor's (UCSF)expense.
Lasers, I thought both companies contributed their own equipment/drug to the trial while UCSF contributes Investigator/medical application/data gathering and analysis.
What's sad lasers is they are two years behind what OncoSec is doing
Hey lasers, I've done some checking but I haven't found any submissions relating to Merck, Oncosec, or UCSF...yet.
From article, "...data from the combination study to be available by mid-2016" is the analyst expectation. I've been hoping for something from ASCO in the first week of June.
To see Dr.Kohrt in action go to:
http://oncosec.com/jmp-immunotherapy-symposium-2015/
and click on the 3 part of the symposium, "In-situ Tumor Vaccination"
I think he made the science easy to understand.
Hey Twiz, I'm guessing from hemophilia complications. Check out this inteview from 2013
www.nytimes.com/2013/12/24/science/a-doctors-intimate-view-of-hemophilia.html
In Memory of Dr. Holbrook Kohrt
I believe he died of complications from his Hemophilia--a bleeding disease. He was only 39.
Dr. Kohrt was an esteemed member of OncoSec’s Scientific Advisory Board and provided valuable strategic insight to the scientific team to develop new therapies in the fight against cancer. OncoSec is dedicated to continuing Holbrook’s legacy by advancing the field of intratumoral immunotherapy to one day benefit patients everywhere. We will remember Dr. Kohrt as a friend, pioneer, and valued member of our team.
“Holbrook was an inspiration to the entire scientific community and relentless in his commitment to advancing his research to help patients,” said Punit Dhillon, President and CEO of OncoSec. “He leaves an incredible legacy as an innovator in the field of immuno-oncology recognized by all of us, as his colleagues who knew him for his passion, sense of humor, and creativity. Holbrook was a brilliant advisor who contributed his considerable expertise to help advance the field of intratumoral immunotherapy and evolve our company. As a friend and colleague, he will be greatly missed.”
Dr. Kohrt made a significant impact in the immuno-oncology field and brought his scientific acumen, insight and passion to every project. He contributed his considerable expertise to help advance the field of intratumoral immunotherapy. Dr. Kohrt was an Assistant Professor at Stanford Cancer Institute, and investigated novel therapeutic strategies to enhance anti-tumor immunity. Dr. Kohrt attended Stanford University Medical School as the Baxter Foundation Scholar, Howard Hughes Scholar, and American Society of Hematology Research Fellow. During this time, he developed, validated, and nationally implemented a nomogram for risk prediction in early stage breast cancer.
Dr. Kohrt trained in Internal Medicine at Stanford University through the Clinical Investigator Pathway and completed fellowship in Hematology and Oncology at Stanford with a research focus on preclinical models of novel immunomodulatory antibodies. He received his Ph.D. in Clinical Trial Design and Tumor Immunology from Stanford. Most notably, Dr. Kohrt along with Dr. Ron Levy at Stanford were academic leaders in the advancement of intratumoral immuno-oncology therapies. Together, they conducted a Phase I/II clinical trial using CG-enriched oligodeoxynucleotide (CpG), a ligand for the Toll-like receptor 9 (TLR9) in non-Hodgkin’s lymphoma. They also demonstrated that intratumoral administration of the checkpoint inhibitor, anti-CTLA-4 antibody, is a safe and effective route of therapy in mice, demonstrating both local and systemic responses.
Hey Guys, I wouldn't make too much of this yet. It really could be an anticipatory figure of speech which reflects all trial data to this date, but without any awareness of present data read out. In fact, that has been Punit's problem, which is to speak about past information as if it were regarding present data, WHICH WE DO NOT HAVE YET! And we start jumping up and down way to early.
Feb.11, 2016 "clinical data supports ImmunoPulse IL-12 and anti-PD-1 as a rational therapeutic combination"
Oct 15, 2015 - "To date data shows that ImmunoPulse IL-12 can generate an initial local ... to support the expansion of R&D operations and increased clinical trial expenses. ..... IL-12 is a rational choice for combination therapy with anti-PD-1"
I would encourage extreme discretion when Punit speaks...
Well I know we get it, but I just wish big-time investors dead – – I can't wait till the science proves with this combo treatment.
From "Oral Cancer News Foundation" - The last Paragraph illustrates the what and why we are hear waitingfor the data from the combination trial and how unique a position OncoSec occupies...
Immunotherapies gaining traction in head and neck cancers
Thu, Feb 18, 2016
Oral Cancer News
Source: www.targetedonc.com
Author: Greg Kennelty
An explosion of immunotherapies is on the horizon for patients with metastatic head and neck cancer, specifically as phase III trials begin to report findings for PD-1 inhibitors. This upcoming wave of new therapies places importance on understanding optimal treatment settings and adverse events associated with these therapies.
In late January, the phase III CheckMate-141 trial investigating the anti–PD-1 agent nivolumab was stopped early, due to a substantial improvement in the primary endpoint of overall survival (OS). The drug was put up against the investigator’s choice of cetuximab (Erbitux), methotrexate, or docetaxel following progression on a platinum-based therapy.
At this time, data from the study have not yet been released but are being prepared for future presentation. Findings from the study are being discussed with the FDA and other health authorities.
In addition to nivolumab, the PD-1 inhibitor pembrolizumab (Keytruda) demonstrated encouraging activity in patients with with advanced PD-L1–positive esophageal carcinoma during the phase Ib KEYNOTE-028 study. Additionally, the agent was effective for patients with squamous cell carcinoma of the head and neck in the phase I KEYNOTE-012 study.
In the head and neck cancer population, the objective response rate with pembrolizumab was 24.8% in 117 evaluable patients. Tumor shrinkage was experienced by 56% of patients and another 25% had stable disease. The response rate seen with pembrolizumab was similar, regardless of HPV infection status. In those with HPV-positive disease, the ORR was 20.6% compared with 27.2% in the negative group.
To gain further insight, Targeted Oncology spoke with head and neck cancer expert Barbara Burtness, MD, professor of Medicine (Medical Oncology), Clinical Research Program Leader, Head and Neck Cancers Program, co-director, Developmental Therapeutics Research Program, Yale Cancer Center.
TARGETED ONCOLOGY: Can you give us an overview of where immunotherapy is currently in head and neck cancer?
BURTNESS: The first trials for immunotherapy in head and neck cancer began two or three years ago and we now have sufficient reason to believe that these therapies are going to be active in the cancer. For example, there is the KEYNOTE-012 trial, which was a trial of pembrolizumab given to an expansion cohort of either HPV-positive or HPV-negative head and neck cancer. The response rate there was about 25%.
There is some reason to believe that if either PD-L1 or PD-L2 are expressed, that that would predict for a higher response rate. There are now phase III trials going forward for both platinum-refractory disease and for first-line patients looking at pembrolizumab compared with chemotherapy.
There are also data with MEDI4736, which if a patient is expressing PD-L1, appears to have a pretty high response rate of about 50% in a small group of patients. There are currently ongoing trials looking at the combination of MEDI4736 with tremelimumab, though we don’t have any data on that just yet.
Then there are novel strategies people have for trying integrate immunotherapy with standard treatment. We have some reason to believe that when head and neck cancer is treated with radiation there is upregulation in tumor-infiltrating lymphocytes and PD-L1. There are trials now moving forward that are integrating immune checkpoint inhibitors together with chemoradiation, or taking patients who have completed their chemoradiation but have persistent disease and exposing them to pembrolizumab in that setting.
The last thing is there is some evidence that siltuximab can upregulate a co-stimulatory molecule, CD137. There are some trials looking at co-targeting EGFR and CD137.
TARGETED ONCOLOGY: What are the side effects in immunotherapy?
BURTNESS: The one thing community oncologists should be aware of is toxicities. As these drugs roll out, these toxicities that will be present are a lot different to manage than the usual cytotoxic agent toxicities. There are a lot of unusual or unexpected side effects that are autoimmune in nature.
The most common toxicity is fatigue. Across all the patients with head and neck cancer who received pembrolizumab, about 17% of them had grade 3 or 4 toxicities. This is a lot easier to tolerate than chemotherapy or chemoradiation. The other things that you might look for are pneumonitis, nephritis, pancreatitis with diabetic symptoms, thyroiditis, and a variety of unusual autoimmune side effects.
TARGETED ONCOLOGY: What do you see as the overall potential for immunotherapy in head and neck cancer?
BURTNESS: Everybody with biomarker expression of either the ligands or the targets in this pathway is likely to be exposed to these drugs in the future. The challenge for us is going to be to figure out, for those patients who are not PD-L1 expressing or who don’t have tumor-infiltrating lymphocytes, other ways that we can prime patients for immunotherapy with our standard treatments. It’s speculative – it’s not something that people are doing in clinics now, but the first trials of those approaches are starting.
There is also ADXS11-001 that is fused to the E7 oncogene from HPV. The idea is that that would increase antigenic presentation and then the immune checkpoint inhibitor could potentially be more effective. That treatment is still in phase I.
"Immuno-Oncology Agents Are Not Above Resistance", Study Shows
(Can you appreciate that we are at such an infancy stage of development in this Cancer Breakthrough? I Think this is exciting to watch this come to fruition. Here, they are still working at supporting T-cell's from becoming exhausted or blocked thru cell adaptation to increase responsiveness to those who respond to treatment, which is important stuff. BUT--NO ONE is doing anything related to turning the MAJORITY of non-responders to Responders--ONLY OncoSec Medical.)
A new study, published in Nature Communications, has delineated a mechanism that could help explain the resistance that is emerging with the new immuno-oncology agents such as PD-1 and PD-L1.
Published Online: February 18, 2016
Surabhi Dangi-Garimella, PhD
A new study, published in Nature Communications, has delineated a mechanism that could help explain the resistance that is emerging with the new immuno-oncology agents such as the inhibitors of programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1). Using immunocompetent mouse models for lung cancer, the authors identified an adaptive immune response—in the form of activated alternative checkpoints—in the tumor microenvironment following anti–PD-1 therapy.
Hey basketball, it's better to pay attention to what kind of conference and not just assume any old conference makes the price go up or down. This conference is not giving data but is presenting what the company is about to investors and fund managers to give them a chance to mull over the material and decide what they're going to do in the future with it . That's a little different than a science conference where they're releasing data results that allows for a more accurate speculation on value to the market – – that's when you have to watch if it's going well or not.
Presentation Stated Development Milestones: Key Value Drivers Over the Next 12 months
--Announce new key academic or industry collaborations
--Expand POC Phase II melanoma combo study sites, complete enrollment and present preliminary clinical data
--Complete TNBC biomarker study as POC in breast cancer, present interim data and finalize development plan
--Announce novel “multi-gene” combination ImmunoPulse candidate
--Present pre-clinical combination data with Heat Biologics
Today's Bio CEO & Investor Conf.,10 AM central time webcast link:
https://www.veracast.com/webcasts/bio/ceoinvestor2016/76113125724.cfm