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Thanks guys, I'm feelin' pretty fired up as we draw close to Nov. 11 & 17!!! Not to mention what follows...
Remember, Data First...Then the Dealing :}
Top 15 Immuno-Oncology Collaborations
September 12, 2016
Alex Philippidis
Biopharma giants have proven willing to shell out billions in collaborations with smaller biotechs aimed at developing new immunotherapies for cancer. [Paul Bradbury/Getty]
Nowhere in biopharma does the adage, “Follow the money” better apply, perhaps, than immuno-oncology, whose market size is expected to balloon to $19 billion in 2019 and $34 billion in 2024 (GlobalData).
With a combined roughly $2.5 billion in sales last year, drugs that harness the body’s immune system as a weapon against cancer have already begun to generate billions. Bristol-Myers Squibb (BMS) immuno-oncology treatment Yervoy® (ipilimumab) surpassed $1 billion in worldwide revenues last year, with BMS’ Opdivo® (nivolumab) close behind at $942 million. Opdivo has already surpassed that total this year, zooming in January–June to $1.544 billion. And while Yervoy slid 19% to $504 million this year due to competition from Opdivo and Merck & Co.’s Keytruda® (pembrolizumab), the two BMS drugs are expected to generate a combined $7.5 billion in sales by 2022, according to Trefis.
Speaking of Keytruda, its $563 million in the first half of 2016 is just $3 million shy of what the drug made all of last year. And Keytruda is expected to leap to $7 billion in sales by 2024 (Research and Markets).
With the potential for billions in new revenues, biopharma giants have proven willing to shell out billions in collaborations with smaller biotechs aimed at developing new immunotherapies for cancer. Earlier this year, the Tufts Center for the Study of Drug Development reported that more than 130 biotechs and 20 pharmaceutical companies were working on immuno-oncology therapies, with the number of collaborations rising to 58 last year from six in 2013.
The largest of these—and several others that were launched this year—can be found in GEN’s list of top 15 immuno-oncology collaborations below. The alliances are ranked by dollar value as disclosed by the companies in regulatory filings, press announcements, and other public statements. Each collaboration is listed by partner names, value, and date announced, followed by a summary, and updates provided by the companies since their launch announcements.
Interestingly, the total value of all 15 ranked collaborations is approximately $30 billion. It’s also fair to say, for now, that the pace of billion-dollar-plus partnership activity is rising, as 2016 has already seen five such collaborations, compared to six last year and four in 2014. However, the list does not include collaborations where details were not disclosed. For example, Novartis and Xencor only revealed the $150 million upfront portion of their partnership to develop bispecific antibodies, announced June 28.
#15. Celgene and Juno Therapeutics
Value: Approximately $1 billion for Juno, including approximately $150 million upfront
Date announced: June 29, 2015
Summary: 10-year global collaboration to develop and commercialize cancer and autoimmune diseases immunotherapies, with an initial focus on chimeric antigen receptor (CAR) technology and T-cell receptor (TCR) technologies. Celgene has the option to serve as commercialization partner for Juno's oncology and cell therapy autoimmune product candidates, including Juno's CD19- and CD22-directed CAR T-cell product candidates.
Updates: On April 28 in announcing first-quarter results, Celgene disclosed that during that month, it exercised its option to develop and commercialize Juno’s CD19 program outside North America and China. The companies agreed to share global development expenses for products in the CD19 program. Celgene agreed to pay Juno a royalty at a percentage in the mid-teens on any future net sales of therapeutic products developed through the CD19 program in Celgene's territories. Celgene entered into a prenegotiated license agreement, with Juno by paying $50 million for the license, Celgene disclosed recently.
#14. Celgene and Agios Pharmaceuticals
Value: About $1 billion-plus for Agios, including $200 million upfront
Date announced: May 17, 2016
Summary: Companies agreed to partner to discover, develop, and commercialize metabolic immuno-oncology therapies, based on Agios’ cellular metabolism research platform. Agios agreed to lead exploratory research, drug discovery, and early development efforts.
Updates: In a July report, Celgene said the collaboration’s initial 4-year term will expire in May 2020, adding: “We may extend the term for up to two additional 1-year terms or in specified cases, up to 4 additional years.” At the end of the research term, Agios said “Celgene may designate for continued development up to three research programs for which development candidates have yet to be nominated, which are referred to as continuation programs.” Agios said it may conduct further research and preclinical and clinical development activities on any continuation program, at its expense, “through completion of an initial Phase I dose-escalation study.”
#13. Eli Lilly and Innovent Biologics
Value: More than $1 billion, including $56 million upfront
Date announced: October 11, 2015
Summary: In expansion of up-to-$456 million cancer therapy strategic alliance announced March 20, 2015, companies agreed to support development and potential commercialization of up to three anti-programmed cell death-1 (PD-1)-based bispecific antibodies for cancer treatments over the next decade, both inside and outside of China. Lilly agreed to exercise rights from the earlier agreement to develop, manufacture, and commercialize these potential cancer treatments outside of China, while Innovent won rights to develop, manufacture, and commercialize the treatments for China, subject to a Lilly opt-in right for co-development and commercialization.
Updates: No subsequent announcements.
#12. Celgene and Sutro Biopharma
Value: More than $1 billion-plus for Sutro, including $95 million upfront (a sum that includes an unspecified equity investment)
Date announced: October 23, 2014
Summary: Companies agreed to advance into immuno-oncology, in expansion of a nearly 2-year-old cancer collaboration originally intended to discover and develop multispecific antibodies and antibody–drug conjugates (ADCs). Expansion doubled the value of the partnership, which was refocused on established immuno-oncology targets such as programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1), as well as new undisclosed targets, using Sutro’s Xpress CF™ and Xpress CF+™ cell-free biologics development platforms. After the initial period, Celgene was given exclusive option to acquire Sutro.
Updates: No subsequent announcements.
#11. Roche and Blueprint Medicines
Value: Up to $1.01 billion for Blueprint, including $45 million upfront
Date announced: March 15, 2016
Summary: Companies agreed to discover, develop, and commercialize up to five small-molecule therapeutics targeting kinases deemed important in cancer immunotherapy. The five could be either single products or products to be combined with Roche therapeutics. Roche will hold options triggered upon achievement of Phase I proof-of-concept for an exclusive license to each drug candidate developed under the collaboration.
Updates: In August, Blueprint disclosed that the partners “have identified targets for three of the collaboration programs, two of which began in the first half of 2016 and the third of which is expected to begin in 2016, and the parties have agreed to work together to use the company’s novel target discovery engine and proprietary compound library to select targets for up to two additional collaboration programs.”
#10. Bristol-Myers Squibb (BMS) and CytomX Therapeutics
Value: Up to $1.242 billion for CytomX, including $50 million upfront
Date announced: May 27, 2014
Summary: Companies agreed to discover, develop, and commercialize new immunotherapies against multiple cancer immunotherapy targets, using CytomX’s Probody™ drug discovery platform. CytomX agreed to grant BMS exclusive worldwide rights to develop and commercialize Probody therapeutics designed to bind selectively to tumors for up to four oncology targets, including the immune inhibitory checkpoint receptor cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). BMS will have additional rights to substitute up to two collaboration targets.
Updates: On January 20, CytomX disclosed its receipt of a $10 million milestone payment from BMS following its selection of a third target in the companies’ strategic oncology collaboration.
#9. Sanofi and BioNTech
Value: Up to $1.5 billion-plus for BioNTech, including $60 million upfront
Date announced: November 3, 2015
Summary: Companies agreed to discover and develop up to five cancer immunotherapies, each consisting of a mixture of synthetic messenger RNAs (mRNAs), using BioNTech’s mRNA formulation technology. BioNTech will also supply part of the mRNA material needed for development activities from its in-house GMP manufacturing unit. BioNTech has the option to co-develop and co-commercialize two of the five mRNA therapeutics products with Sanofi in the EU and the U.S.
#8. Baxalta and Symphogen
Value: Up to €1.4 billion (approximately $1.6 billion) for Symphogen
Date announced: January 4, 2016
Summary: Companies agreed to develop Symphogen’s portfolio of early-stage immuno-oncology programs, including new treatments against six undisclosed checkpoint targets, with the first program to enter clinical studies in 2017.
Update: On June 3, Baxalta became an indirect wholly owned subsidiary of Shire following completion of the companies’ $32 billion merger. Symphogen CFO and Deputy CEO Martin Olin told GEN that the collaboration is still in effect.
#7. Baxalta and Precision BioSciences
Value: Up to $1.7 billion for Precision, including $105 million upfront
Date announced: February 25, 2016
Summary: Companies agreed to develop allogeneic chimeric antigen receptor (CAR) T-cell therapies, by bringing together Baxalta’s immuno-oncology candidates with Precision’s ARCUS genome editing platform technology. Baxalta and Precision agreed to develop CAR T-cell therapies for up to six undisclosed targets, with the first program expected to enter clinical studies in late 2017. Companies said the CAR T-cell therapies will address areas of major unmet need in multiple unspecified cancers.
Update: On June 3, Baxalta became an indirect wholly owned subsidiary of Shire following completion of the companies’ $32 billion merger.
#6. Bristol-Myers Squibb (BMS) and Five Prime Therapeutics
Value: Up to $1.74 billion for Five Prime, including $350 million upfront
Date announced: October 15, 2015
Summary: BMS agreed to co-develop and co-commercialize Five Prime’s colony-stimulating factor 1 receptor (CSF1R) antibody program, led by the Phase I cancer/immunology compound cabiralizumab (FPA008). BMS agreed to oversee development and manufacturing of cabiralizumab for all indications, subject to an option by Five Prime to conduct and pay for future studies to support approval of cabiralizumab in pigmented villonodular synovitis (PVNS) and cabiralizumab in combination with Five Prime’s internal pipeline assets in immuno-oncology.
Update: On May 12, Five Prime said cabiralizumab was advanced into the Phase II dose-expansion portion of the ongoing Phase I/II trial in PVNS. Cabiralizumab was granted the FDA’s Orphan Drug Designation for PVNS in January 2016.
#5. Sanofi and Regeneron
Value: Up to $2.17 billion for Regeneron, including $640 million upfront
Date announced: July 28, 2015
Summary: Sanofi and Regeneron agreed to jointly develop REGN2810, a programmed cell death protein 1 (PD-1) inhibitor currently in Phase I and launch clinical trials in 2016 with new therapeutic candidates based on ongoing preclinical programs. The partners committed to spend $325 million each toward developing REGN2810.
Update: In releasing second-quarter results August 4, Regeneron said REGN2810 had entered a potentially pivotal clinical study for the treatment of advanced cutaneous squamous cell carcinoma during Q2.
#4. Celgene and Jounce Therapeutics
Value: Up to $2.6 billion for Jounce, including $225 million upfront and a $36 million equity investment by Celgene
Date announced: July 19, 2016
Summary: Celgene received options to develop and commercialize jointly cancer immunotherapies that include Jounce’s lead candidate JTX-2011, a monoclonal antibody expected to enter clinical trials by year’s end, and other cancer immunotherapies. Celgene gained options from Jounce for up to four of its early-stage programs to be selected from a defined pool of B-cell, regulatory T-cell, and tumor-associated macrophage targets emerging from the Jounce Translational Science Platform; also gained was an additional option to share a checkpoint immuno-oncology program equally with Jounce.
Update: In July, Celgene disclosed that the collaboration agreement had an initial term of 4 years, which may be extended up to 3 additional years.
#3. Merck KGaA and Pfizer
Value: Up to $2.85 billion for Merck KGaA, including $895 million upfront
Date announced: November 17, 2014
Summary: Merck KGaA agreed to jointly develop and commercialize its programmed cell death ligand-1 (PD-L1) checkpoint inhibitor MSB0010718C (since renamed avelumab and also known as PF-06834635) with Pfizer, both as a single agent and in various combinations with the companies’ oncology therapies.
Update: On July 6, the companies said they launched the Phase III JAVELIN Ovarian 100 trial. The trial is intended to assess avelumab in combination with, and/or as follow-on (maintenance) treatment to, platinum-based chemotherapy in patients with locally advanced or metastatic disease (Stage III or Stage IV) with previously untreated epithelial ovarian cancer.
#2. Pfizer and Cellectis
Value: Up to $2.885 billion for Cellectis, including $80 million upfront
Date announced: June 18, 2014
Summary: Pfizer and Cellectis agreed to develop chimeric antigen receptor (CAR) T-cell cancer immunotherapies directed at select targets using the French biotech’s CAR T-cell platform technology. Pfizer has exclusive rights to develop and commercialize CAR T-cell cancer therapies directed at a total of 15 targets of its choosing. Both companies agreed to work together on preclinical research for four of 12 additional targets to be selected by Cellectis, with Pfizer having the right of first refusal to the four.
Update: On June 20, Cellectis said the first patient was dosed in a Phase I study of UCART19 in pediatric acute B lymphoblastic leukemia. UCART19 is an allogeneic CAR T-cell candidate for CD19-expressing blood malignancies, gene edited with Cellectis' TALEN® technology.
#1. Merck & Co. and Ablynx
Value: €5.78 billion ($6.4 billion)
Date announced: July 22, 2015
Summary: In an up-to-€4.08 billion (about $4.5 billion) expansion of an up-to-€1.7 billion ($1.9 billion) immuno-oncology collaboration to address additional checkpoint modulator targets, announced February 3, 2014, the companies agreed to discover and develop up to 12 additional cancer drugs based on single-domain antibody fragments, or Nanobodies®, through preclinical proof-of-concept. After that, Merck will have the option to advance specific lead candidates. Merck will also oversee clinical development, manufacturing, and commercialization of any products resulting from the collaboration, which grew to 17 Nanobodies programs.
Updates: On October 15, 2015, Ablynx said preclinical proof-of-concept was achieved with a bispecific Nanobody program developed through the Merck & Co. collaboration, triggering a €3.5 million ($3.9 million) milestone payment to Ablynx.
If You Like Inovio Pharmaceuticals, You'll Love This Company (ONCS, INO)
Inovio Pharmaceuticals Inc. (NASDAQ:INO) and OncoSec Medical Inc. (NASDAQ:ONCS) are working on the same biotechnology for the same reason, though each has a different endzone in mind.
By James E. Brumley
The term electroporation isn't exactly a term commonly thrown around at the dinner table or around the water cooler. In fact, it's such a rare thing, the average person has likely never even heard of it. It's an idea that's caught the attention of a couple of publicly-traded companies, though, and a handful of academic researchers. The two companies in question are Inovio Pharmaceuticals Inc. (NASDAQ:INO) and OncoSec Medical Inc. (NASDAQ:ONCS), and though they have their similarities, for investors, they're different enough to merit distinguishing.
But first, what's electroporation? In layman's terms, it's the application of an electrical current to living cells to widen their porous openings, which in turn lets certain medicines into them where they may have more - or even some - effect.
It is in many regards the next evolution of medical science.
The advent of DNA-based therapies is only as meaningful to the degree an engineered virus or genetic code can enter into a cancerous cell and rewrite its code to either program it to die, or two "wire" it so a body's immune system can kill it. Many of these medicines simply wash around a cancerous cell without ever actually penetrating it, renderings them pointless. By opening up a diseased cell and letting particular treatments into the cell in question, however, allows a medicine to work to its fullest extent.
Based on that science, a company called Inovio Pharmaceuticals has combined the process of electroporation with its SynCon(r) DNA plasmid technology.
The concept is simple enough - take the genetic code for a vital element of the immune system or immune response and create a significant production of it inside the body. Its products aim to create disease-specific cytokines that put an immune system in a higher gear with more potent weapons.
Inovio Pharmaceuticals presently has fifteen trials underway, most of which are in phase 1 trials. It's an impressive number to be sure, but also an expensive one just due to the sheer number of tests the company must manage. And, regardless of how many of the fifteen drugs make it to the market, most of them are still well away from an approval in terms of time.
That's in contrast to OncoSec Medical, which is focusing primarily on melanoma. Two of its four clinical trials underway now are taking aim at the dreaded skin cancer, another is aimed and head and neck cancer, and the fourth is seeking to treat so-called triple-negative breast cancer.
These are the perhaps the biggest underserved markets on the cancer front, largely because they've been the most difficult to treat; many companies don't even bother trying to top the current standard of care.
The reason and result of the super-tight focus OncoSec brings to the table is making sure it allocates time and resources where it has the best shot at making a meaningful dent. To that end, it's focusing on one narrow but important sliver of the cancer immunology market.... DNA-based interleukin-12 (IL-12), a naturally occurring protein with immune-stimulating functions. The treatment is designed to produce a controlled, localized expression of IL-12 in the tumor microenvironment, which in turn, enables the immune system to target and attack tumors throughout the body.
And so far, its melanoma results have been very encouraging. In phase 2 trials, the combination of ImmunoPulse and IL-12 created a response in 48% of melanoma patients, and drove a complete response in 14% of patients.
Those are compelling results for a disease that's often simply ceded to a "let's just do the best we can probably do" kind of mentality from the medical community using the current standard of care to treat melanoma patients.
In other words, for investors, the "less is more" philosophy means ONCS a better focused, smaller, more nimble way to play the budding field of electroporation.
To Choney: a respected article from a former ihub board mediator
OncoSec Medical: A Look Back, And A Look Forward
Feb. 16, 2016 8:30 AM ET
About: OncoSec Medical Incorporated (ONCS), Includes: HTBX, PKI
Shallum Furbush
OncoSec has had to evolve with the developments in immunotherapy, changing focus from developing mono-therapies to combination therapy.
The ability to deliver multiple genes directly into a cell has the potential to radically change the direction of immunotherapy in the future.
Roughly 70% of all Melanoma patients will not respond to Anti-PD-1 drugs, OncoSec can change that.
OncoSec is currently valued below cash on hand.
"I always like to say that my job is about three things, to remove obstacles for people, to keep the company moving forward, and to make sure it is funded" Punit Dhillon
Have you ever bought stock in a company prematurely, or purchased a stock that looked promising, only to have advances in the industry cause strategic changes within the company delaying your investment? Chances are if you have not yet experienced this, you will. This has been the case for me with OncoSec Medical (OTCQB: ONCS). Since 2013, when I initially invested in the company, I have been following their progress as they have continued to grow and develop. It has not been a smooth ride, at times appearing to be a mistake, while at other times remaining a promising investment.
When I first invested in OncoSec the share price was at $0.17 ($3.40 post reverse split) and I have held it while it dropped more than 50 percent, falling more than 80 percent from its 52-week high. Everyone who invests knows what it is like to watch a stock take a significant drop. It hits you right in the gut, and makes you question your own judgment. Even though you know that emotions are not supposed to be involved, it is a challenge to detach yourself and remain objective. Buying too early, however does not necessarily mean you bought the wrong stock. It cannot be stressed how important it is to reevaluate a decision before taking action. Rather than simply declaring a stock "junk" and taking the loss, revisit your reason for owning it first. That's where I found myself as last year closed.
When a stock I have invested both time and money in takes that kind of a hit I need to know what happened. Debrief before making a decision. Was I lax in my due diligence? Was the original theory wrong, or was there a disconnect somewhere? Ultimately what I want to know is: Why did the stock drop? What should I have done differently, if anything? Is it still a good investment?
So, as part of my reevaluation I called Punit Dhillon, CEO of OncoSec, with a list of questions I had developed that expressed my concerns, not just about the stock price, but the overall direction of the company, and its management. I wanted to understand the mindset of the company, how they intend to move forward and at what pace. Over the course of two weeks, our conversations helped to reaffirm my confidence in the direction OncoSec is going, but it also made it clear that this will be a longer road than I had anticipated.
Some of the questions I had were not unique:
Why aren't you starting Phase 3 trials with ImmunoPulse now?
Is Dr. Robert Pierce (Chief Scientific Officer) going to quit?
Why is your cash burn rate so high?
How many more dilutions before we see some value?
What makes ImmunoPulse valuable? How will you leverage that value?
Mr. Dhillon was familiar with these, having been asked the same things from many investors. What I learned is that few people really seem to understand what OncoSec is focused on, why, and what affect that has on their future potential. In the knee-jerk response to a depressed stock price many are willing to throw the proverbial baby out with the bath water. As an investment OncoSec's potential is impressive, and many investors who either do not understand that potential, or are more concerned with immediate returns, may be missing a great opportunity here.
Why did I choose OncoSec Medical?
Originally I was drawn to invest in OncoSec because of their ImmunoPulse technology, an electroporation platform with the ability to deliver any combination of genes to any location in the body. Using an electric pulse, this technique allows the membranes of cancerous cells at an injection site to be temporarily opened so that gene strands can be introduced directly into those cells. This intratumoral approach coupled with Interleukin-12 (IL-12), a drug proven to increase Tumor Infiltrating Lymphocytes (NASDAQ:TIL), CD8+ and Interferon gamma, has shown great promise. These biomarkers are known to be key indicators for determining who will respond to Anti-PD-1 drugs like Bristol-Meyers Squibb's (NYSE: BMY) Opdivo and Merck's (NYSE: MRK) Keytruda (see article: PD-1 blockade induces responses by inhibiting adaptive immune resistance from nature). An increase in these biomarkers will lead to greater immune response, and thus a higher response rate to treatment. This should lead to effective treatment opportunities across multiple indications. But the timing wasn't quite right.
Nothing has changed in the science, in fact with multiple trials ongoing or completed in five different types of cancer, with all available data showing consistent response to therapy with increases in TIL, the stock is still appealing - perhaps even more so now at this discounted and undervalued price. But why is it undervalued? In my opinion, there are several reasons, some of which are shared by Mr. Dhillon, including: incorrect assumptions by under-informed investors, several changes in development direction, which although positive in the aggregate have slowed the clinical trial process, the company not following a "traditional process" for a biotech company, poor guidance and communication from the company, and external factors that have had a net negative effect on the share price. So let's break some of these down.
A New Direction and its Consequences
"we can move really quickly, and at the same time that has hurt us because of our nimbleness people haven't been able to keep up with our development. Here we went out of the gate with NeoPulse and ImmunoPulse, two different platforms altogether, and two different pipelines and we were out there trying to define ourselves and two years later we are focusing on ImmunoPulse and IL-12, and a year later we are telling people it works well with Anti-PD-1, and now we are waiting for the data. I think we loose our credibility, its a constantly shifting story without the explanation of why. You can keep saying this is the hypothesis, for only so long till someone says hold on you keep shifting and not giving us a reason why." Punit Dhillon
Let me begin by saying that OncoSec is a company that allows the results of their research dictate the direction they go. Unfortunately they are also a company that does not issue a press release for every decision they make.
When I first invested in OncoSec they were pursing a mono-therapy application of IL-12 with ImmunoPulse for three indications, Melanoma, Merkel Cell Carcinoma, and T-Cell Lymphoma. The potential looked good and their was an expectation that the stock price would rise as those trials, then in Phase II, moved forward into Phase III. However, the industry changed and with it the development strategy.
"It would be futile for us to move forward on IL-12 as a mono-therapy in melanoma, maybe its a product in terms of a certain population but its going to take a long time to get approved and take a lot of resources and it doesn't have much chance of success in terms of the overall landscape in melanoma" Punit Dhillon
Changes in the immunotherapy industry, specifically the introduction of Anti-PD-1 drugs, with their impressive results, changed the direction of immunotherapy. OncoSec then found itself faced with a tough decision, it could continue pursuing a mono-therapy with limited market application, or follow the new direction of the industry. Choosing to follow the industry they redirected their limited resources, seeking to develop a new use for their Immunopulse technology, in combination therapies. This required OncoSec to abandon the path they had been pursing mid-stride.
The abruptness of this change in direction, and the lack of clear information, unfortunately left many investors, myself included, unaware that the new combination trials would not be carried out in addition to existing research. When I realized the nature of the changes I did not foresee the delay this would bring to developing a product many investors thought was in the homestretch. The projected timeline released by the company proved overly optimistic. Suddenly expectations about direction, valuation, and expected trial results were no longer valid, leaving many confused disappointed, and angry.
The Phase II trials had become merely the first step in a longer process, and OncoSec was now effectively, a pre-clinical biotechnology company, and it should have been valued as such. The new combination trials required funds, as did continued operations and research, leading to several rounds of dilution. Without a catalyst to support the price, institutional owners chose to sell, holding onto their warrants from the sideline, while the share price dropped.
It then took over 18 months from the first mention of a combination trial to its first patient enrollment. There is a process, and in that process companies do not have control over the timeline. Through poor guidance the expectation was created that the trials would begin in January 2015. They did not start until seven months later, in July. During this time investors speculated that a partnership deal was in the works, one that would include cash to cover expenses for the trial, though there never was such a deal the heightened expectations led to disappointment when the actual details of the trial were finally released. Investors viewed this as a failure.
The trial, a Phase IIb clinical trial on Melanoma, would be designed as an open label Investigator Sponsored Trial (NYSEARCA:IST), a collaborative effort with the University of California, Los Angeles (UCLA), and Merck. This IST was not what was hoped for and had the unfortunate effect of damaging investor confidence. In addition, for the investor the lack of a partnership meant little chance of seeing any return on their investment, instead they had a long wait ahead of them.
For the company the nature of the trial is a boon, allowing OncoSec to retain ownership of their product. In the meantime the company has undergone two more rounds of dilution, as the overall biotech sector has seen deterioration, creating the perfect storm to repress and hold low the company's share price.
All of these concerns, though valid, must be kept in perspective, considering:
The time frame for the trials is not out of the ordinary.
Investor expectations were faulty in many ways partly due to poor communication from the company, but primarily due to speculation.
The frustration with the lack of a partnership is a result of assumptions by investors who expected the company to behave in the predictable manner of other biotech companies, a failure on the part of the investor not the company.
Deterioration of the market is a byproduct of being listed in an underperforming sector, not necessarily a flaw in the individual stock itself.
It is because I believe these to be for the most part either irrelevant factors, or those based on incorrect assumptions that I believe there is a window of opportunity here for the informed investor.
The Phase IIb Clinical Trial
"the way that our platform is truly differentiated compared to anybody else out there is the fact that you can stack multiple genes and drive an immune response intratumorally and expose the body to those cancer cell antigens faster. I think that is lost on a lot of people and that is why our pipeline is so laser focused on addressing the acute opportunities like IL-12 in Melanoma" Punit Dhillon
This is the make or break trial for OncoSec, and they are very aware of that fact. The design of the IST itself reflects that fact. A combination trial using patients who have been pre-screened, through the use of tumor biopsies, accepting only those who show either no, or low TIL. This is unique in that they are seeking only patients who are expected to have little or no response to Keytruda. The idea being that if these patients respond to the combination of Keytruda and ImmunoPulse IL-12, it will show the ability to turn non-responders into responders - a huge unmet medical need in oncology, as up to eighty percent of the population are non-responders for Anti-PD-1. Because only patients who are the least likely to respond to Keytruda will be enrolled any positive results will be significant.
This is important because there is no other combination trial, that I am aware of, that is weeding out responders of Anti-PD-1 from their enrollment. As a result, OncoSec could wind up with the only FDA approved therapy for patients who test as non-responsive to Anti-PD-1. Keep in mind that an "apple-to-apple" comparison cannot be made between OncoSec's trial and other combination trials (since approx. 20-30% are ineligible). Due to the nature of this a 25-30% response rate here could equate to a 50% response rate in another trial, once adjustments for eligibility are made. This sets the bar high and OncoSec expects to meet the challenge.
As part of all trials PerkinElmer (NYSE: PKI) in collaboration with OncoSec will be testing the effectiveness of their device, the Vectra Quantitative Pathology Imaging System, at differentiating which patients are refractory to Anti-PD-1 therapy. The accuracy of PerkinElmer's device will be established by comparing its results to those obtained by traditional biopsy test results. If this device is determined to be accurate it will provide a faster method for determining if a patient will respond to Anti-PD-1 therapy. This would allow oncologists to make treatment decisions for initial non-responders more quickly in the future decreasing the time from diagnosis to treatment.
Where the development timeline is concerned it is also important to note that the IST need not be completed prior to starting a Phase III Registration trial. In fact, OncoSec is already in the early stages of planning a Registration Trial, with the goal of a start date in the first quarter of 2017. Additional information on this trial is expected later this year after interim results from the IST and performance results of the PerkinElmer device are released.
The Path to Profitability
The Phase IIb Melanoma trial I have just described is not only a proof of concept, but also the path to profitability for the company. It will provide the data OncoSec will need in order to pursue a meaningful partnership and to initiate a Phase III registration trial. Positive results from this trial should stir up interest among other potential partnerships as well, leading to further collaborations - not to mention increased potential for attracting additional institutional investors. It is said of money that "the first million is the hardest" and this is true of partnerships as well, the first partnership with a company willing to put money on the table is always the most difficult to get.
So far the scientific evidence from early trials supports my belief that the combination treatment OncoSec has developed will work, however, until it has been proven it remains theoretical. Solid trial data and concrete results are the path to that first partnership, a path I believe OncoSec is traveling. Time and data will tell.
Currently trading with a market cap below cash on hand, it is no secret that the share price has been in decline and remains unattractive based on past trends. However, I would suggest that upcoming interim results from the Phase IIb trials are likely to provide a strong enough catalyst to reverse those trends and create upward momentum providing significant returns. The obvious questions remain: When will those results be released? And will they be enough?
Attempting an educated guess at answering the first question, I offer the following: The trial itself consists of a treatment regiment of one year, even with complete responders a minimum of six months of treatment is required. As of October 1st, 2015, out of the 42 patient "slots" 8 patients were enrolled, the first in mid-July 2015. Which means that at the earliest data from these eight patients could be available by March; this assumes an astounding complete response from all eight currently enrolled patients. A more realistic view, using the full one-year treatment regiment, is that interim data will be released sometime after July. As for trial completion, final enrollment is projected to occur late in 2016, which means a completion time frame around the third quarter of 2017.
Feeling comfortable with the accuracy of that assessment, I can move on and take a look at where the company is today. Is OncoSec a company I want to stay invested in? If so should I increase my position? Or is it time to take my losses and sell?
If I did not own it already would I buy it now?
This is a question every investor should ask when they are considering dumping a stock. It is the essential question you must answer if you want to know whether or not you remain confident in a particular investment. This is the question I must answer, so let's look at the facts:
Current Market Cap: $26.22 Million
Shares Outstanding: 16,971,214
Warrants: 1,895,102 (many to expire soon)
Cash on hand: $33 Million (as of Dec 31, 2015)
Current Burn Rate: $1.6 - $1.8 Million per Month
Institutional Holdings:Estimated at 20% (not all are required to report)
Insider holdings: 12%
Current share price aside, what I see is a company that is moving forward in its product development.
Not merely focused on Melanoma, OncoSec has added trials for indications in Triple Negative Breast Cancer (TNBC) as well as Head and Neck Cancer. These will determine whether IL-12 can be used to drive an immune response in cancers beyond Melanoma. These trials should lead to future opportunities, expansion of their clinical pipeline, and increase partnership potential. To this point, OncoSec has already engaged in pre-clinical collaborations with Heat Biologics (NASDAQ: HTBX) and Plexxikon (a member of the Daiichi Sankyo Group [ OTCPK:DSNKY]).
With regard to the Triple Negative Breast Cancer (TNBC) trial, a ten patient clinical trial, OncoSec is simply attempting to show the ability to increase TIL in these patients. This is being done in preparation for a future ImmunoPulse combination trial using what Mr. Dhillon refers to as a "novel gene combination". At this point no details are available about this gene.
During this time the company itself has grown, adding personnel positions in both its administration and research departments. Consolidating its operations into one building, OncoSec negotiated a deal that includes a year of free rent with Alexandria, a Real Estate Investment Trust (REIT), for office and laboratory space. This decision has allowed the company to reduce operating overhead while increasing the square feet of operations.
Finally, where leadership is concerned, although there has been a small amount of turnover, Punit Dhillon CEO, and Dr. Robert Pierce, the Chief Science Officer CSO, remain fully committed to this company. Mr. Dhillon said they are expecting to add additional key personnel in the near future as the company continues to grow.
So What's the Verdict?
After looking over everything that OncoSec has done as a company I still believe they are a good investment, certainly better now than when I first bought. It is obvious that I initially bought in too early, but I believe this company will ultimately be a profitable investment, albeit on a much longer timeline than I had anticipated.
Final Thoughts
"making sure we are clear on expectations and making sure we get investors for the right reasons" Punit Dhillon
I won't be selling but I don't expect to see immediate profitability either. Market conditions remain bearish and the wait for a substantive catalyst may see further depression of the share price. Overall my greatest complaint, and one that the company can correct fairly easily, is the lack of guidance. I realize the objective is to let the science be its own voice but investors like to know what is happening - especially when the answer is nothing. A commitment from management to develop better communication would go a long way toward repairing the distrust many long-term investors have built up with over the years. Mr. Dhillon understands this and says he is aware of the breakdown and the company is making an effort to correct it going forward.
Funding also remains a concern, and even though Mr. Dhillon told me he believes that the cash on hand can last until the second quarter of 2017, I have some doubts. If the cash burn increases, or there are unforeseen expenses, OncoSec may be forced to undergo another dilution before a substantial catalyst occurs.
Something else I'd like to see is a "guide for the layman" explaining to the investment world (non-scientists) what the data means when it is released. How can I know if the response rate is good, great or a disappointment? How can I compare that to another combination trial (e.g. The Bristol Meyers Squibb trial of Yervoy and Opdivo)? How do I compare it to aspects of other trials like a relatively small study of Durvalumab and Tremelimumab published by THE LANCET Oncology, wherein one small cohort of the study that tested negative for PDL-1 had a twenty-nine percent response rate?
Having reaffirmed my reasons for owning stock in OncoSec Medical I will continue to hold the shares I currently own. Though I have no intention to purchase more in the next 30 days, I expect I will purchase additional shares during the 2nd half of the year.
Ultimately a decision to Buy, Sell, or Hold, is one that each investor has to make on his own. I hope sharing my thought process will help you make your own decision.
Projected Time Line
With the exception of the two noted trials*, which the company has acknowledged, this list is my own creation: It does not reflect, nor should it be assumed to imply knowledge of official plans or timelines by OncoSec Medical, locations listed are based on my assumption that data will be released at the same conferences they have released data at previously. (**These are highly speculative on my part.)
May 2016: Heat Biologics pre-clinical data at PEGS
May 2016: Head and Neck Phase II Clinical trial interim data at ASCO**
May 2016: Expanded Melanoma Phase II Clinical trial interim data at ASCO**
3rd Qtr 2016: Plexxikon pre-clinical combination trial data (only if significant)
Sep 2016: Melanoma Phase IIb interim results from IST - at Second World Congress of Electroporation, or European Cancer Congress
Dec 2016: Second round of Phase IIb interim results from IST, likely at announcement of final patient enrollment - at Melanoma Global 2016
Dec 2016: Announcement of Partnership for Phase III Registration Trial at Melanoma Global 2016
3rd or 4th Qtr 2016: Triple Negative Breast Cancer enrollment completion
4th Qtr 2016: Heat Partnership announcement for Phase I trial (dependent on pre-clinical trial results)
Late 1st Qtr 2017: Phase III Melanoma Registration trial*
Late 1st Qtr 2017: Triple Negative Breast Cancer Phase Ib trial* (with IL-12 and Novel drug)
Plexxikon Partnership for Phase I trial (timeframe remains unclear)
Announcement of additional key collaborations with academic and industry partners. OncoSec is not discussing this area but I would expect to begin seeing these before the end of 2016 in preparation for future trials.
Disclosure: I am/we are long ONCS.
I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it. I have no business relationship with any company whose stock is mentioned in this article.
Editor's Note: This article covers one or more stocks trading at less than $1 per share and/or with less than a $100 million market cap. Please be aware of the risks associated with these stocks.
Ahhh, thanks TJ
From the PR:
Abstract Title: Phase II Study of Intratumoral plasmid Interleukin 12 (pIL-12) with Electroporation in Combination with Pembrolizumab in Stage III/IV Melanoma Patients with Low Tumor Infiltrating Lymphocytes (Abstract #203921)
Lead Author: Alain Algazi, MD, Clinical Instructor, Department of Medicine (Hematology/Oncology), UCSF
Poster Number: 466
Date and Time: November 11, 2016 at 12:15 pm EDT (Oral poster presentation to be defined)
Location: Prince George's Exhibition Hall AB, Gaylord National Resort & Convention Center
So no booth at the SITE...I guess the Oral presentation on Friday, Nov. 11th (just 13 days) at 12:15 is enough.
I also noticed Dr. Algazi's opening oral, it looks like, is first up to bat, since the doors open at 12 noon.
If you would like a sample of Dr. Alain Algazi's presentation abilities, check out his presentation from May 7, 2015 of last year.
Wish I could be there!!!
[url]
Hi Titan , I find it interesting that big Pharma would invest 500 million upfront for a small combination drug to chemotherapy which over the next 10 years is going to be reduced vastly in its treating patients due to the advancements of immunotherapy. To me that begs the question what the valuation would be for a combination drug in the burgeoning market of immunotherapy which is going to occupy 60% of cancer treatment in general over the next 10 years?
Hey, $5 sounds pretty damn good right now!
Yes, PD-L1's have the same % of non-responders
chick, I am so with you on this, BUT--I think the problem comes in the practical business decisions that big Pharma faces. They have to consider taking on the challenge of production, distribution, training/usage of device, and maintenance of the electroporation device. They also have there finger on the pulse of global clinical developments in drug development.
They have a window into things like, "mechanism of change", and are always looking for an approach that is non-device oriented (cheaper to manufacture and distribute), since that creates complications when compared to a drug that requires little training, simpler production/implementation, and maintenance/storage, with the potential to equal or surpass the major investment in a platform which they may see as obsolete in too few a years as to justify an investment at this time---given the insider information that they have from their multiple trials.
I have researched the small percentage of companies that make it past the P3 trial. Companies that never get "picked up" or are simply left to die if it is not recognized. I've also seen companies that are picked up by big pharma just to keep a short term advantage (which may be how other companies see OncoSec at this time) just to keep it out of their competitor's hands (meaning other PD-1/PD-L1 drugs.
Lots of ambiguity hear until OncoSec can MAKE THEIR CASE to to both the scientific and investment communities--They have reached another truly "make or break" moment in cancer research history. And the odds are seriously stacked against them--which is why the risk/reward ratio is to amazingly high. This the biggest gamble on these processes that I have every made. I am still long and strong but knowing there is know guarantee here But amazing potential if OncoSec is far enough ahead of competition to make their platform worth the investment to big phama--all things considered.
I don't think that's right HC, that was their price target a year ago – – but it hasn't been that for a long time and I can't find any analyst report with a $25 price target published in the last month. I am hopeful that they will return back to those levels following the November 17th symposium.
I think Chick that there were investors and analyst that were present at the fourth quarter release phone cast that we got to listen into, it was verbally stated that they were impressed with the data that they're coming up with and that's why they were leading to amending the trial. Not exactly sure what that entails but the doctor made it sound like the trial could be much more effective in facilitating more information.
But as far as November 17, it's important that the analysts get a revised understanding of the potential that is out in front of Oncosec with this Endoscopic electrogene transfer device and it's impact on future revenue producing potential by reaching nonresponders across multiple indications – – the the value this adds to the company will add to it's worth either in a buyout circumstance or licensing deal.
I don't believe that's priced into the present valuation the analyst have for Oncosec, and I think following after their visual webcast and their two hour presentation with new timelines, new molecules, new clinical trial, new device potential understood-- then I'm guessing the analyst will have ample information to revise Oncosec's target PPS value upwards.
I think that's important from a business standpoint because are also seeking to raise money for their future clinical trials in which case they may also then have to take a hit on the PPS for doing so. So I think from now through at least February this could be a very interesting ride.
Wish you'ld talk like that more often hschlauch. That is exactly what the analysts and investors need to hear and understand more clearly. A comparative analysis like that is important and understanding of toxicity with the other trials and understanding of the mechanisms of change that are not as effective--All that in contrast to The effectiveness of the mechanism of change which the ImmunoPulse platform utilizes and the low to no side effects.
Regarding the melanoma mouse trial though: the conclusions are as follows – –
CONCLUSIONS
The Helical integrated applicator is a novel device which allows the immunotherapeutic gene delivery of tumors up to 10cm into tissue through minimally invasive means, such as a trocar or endoscope. The helical injection needle provides the dual benefits of increased DNA distribution for more effective gene delivery and tumor anchoring for reliable treatment of compliant tumors. These characteristics yield enhanced efficacy of IL-12 plasmid electroporation in an aggressive B16F10 melanoma model, with improved tumor growth control and survival with a single treatment. This device will allow the application of intratumoral IL-12 gene immunotherapy to a broad range of deep tissue cancers. (from OncoSecs's poster presentation)
The next major technological hurdle for Oncosec.
I've been passionate about this Company since November 2011, but the focus of that passion has shifted several times due to technological advancements over the years. I started talking about it on this board in 2012. Back then the big deal was the use of electroporation plus a chemotherapy drug called Bliomycin. But then immunotherapy worked its way into the arena where Punit advanced a new platform to adapt and compete in this field. Only to then find out that the results were not significant enough to take it forward as a monotherapy and time kept ticking away…
Then in 2014 two things Burst onto the scene almost simultaneously – – Mercks drug, Keytruda and Dr Robert Pierce who showed up on Oncosec's doorstep from Merck Research Labs where he was the Executive Director/Member of the Global Anti-PD-1 (Keytruda) Development Team.
His insight into interleukin 12 and it's ability to turn nonresponders into responders put Oncosec's potential for tremendous gains be back out in front of the pack, but no longer has a monotherapy… They now require a combination in order to succeed. But now even this track is under drug development pressure as others, as being discussed on this board, are nipping at the hills of turning nonresponders into responders. And remember, this is only in one indication that has been demonstrated with safety and efficacy – – and that is in melanoma only. This is because they've only been limited in their technology to treat tumors at the epidermal level only – – meaning only on the surface of the skin. In other words they are a one trick pony.
A partnership Involving only this indication of melanoma, however significant and meaningful for those suffering from melanoma cancer, would provide a short lifespan for OncoSec's ImmunoPulse platform. They have been scrambling for the past year and a half to develop a subcutaneous go-anywhere catheter system to stay viable, which apparently seems to have gone relatively unnoticed in it's ability to treat tumors below the skin level, i.e., soft tissue tumors, such as would exist on bladders, livers, lungs, inside head and neck areas.
What I think is interesting is the timing between Keyruda's FDA approval for these particular indications, (excluding liver), and OncoSec's foresight a year and a half ago to begin the research and development for the go-anywhere technology. But ONCS has yet to demonstrate in human trials, their ability to take the ImmunoPulse platform to those internal locations--and to me this is absolutely crucial if they are to be more than just a one trick pony and find themselves with only one cancer indication that they can treat in their basket.
I'm not trying to be a wet blanket here, but I would think that would give any major pharmaceutical pause when considering partnership or ownership at this time with OncoSec… Or am I missing something?
It seems to me the emphasis is not on the particular mechanisms of treating the tumor with regards to the ImmunoPulse platform, I for one, believe that we are going to see data that will demonstrate why they are in the prime position in the field of melanoma. But it is the threat to OncoSec's timing in the market and being able to find a partner or a potential buyer without having demonstrated a significant safety and efficacy profile for their go-anywhere device, which up to this point in time they do not have except in mouse trial data only – – which does demonstrate comparable results with the ImmunoPulse platform at the cutaneous level in humans.
I am assuming the investor and analyst day, November 17 will be discussing the timelines that would include the human clinical trials involving their new go-anywhere device, to include the need for a partner or the need for raising money to accomplish this on their own – – simply because time is of the essence in this rapidly developing technological field. it is this area partnering/financing that I think is the next technological hurdle--The validation of this go-anywhere device
Merck's Keytruda succeeds in key bladder cancer trial
Health News | Fri Oct 21, 2016 (It looks to me like Merck can add Bladder Cancer to it's approval list along with melanoma, head and neck, and lung cancer)
Merck & Co Inc said its immunotherapy, Keytruda, helped previously treated patients with advanced bladder cancer live longer in a late-stage study, prompting an independent monitoring panel to recommend stopping the trial early.
The blockbuster drug's benefit in patients with urothelial cancer, the most common form of bladder cancer, surpassed that of chemotherapy, meeting the main study goal of overall survival.
Bladder cancer occurs when cells in the urinary bladder start to grow uncontrollably. Urothelial carcinoma starts in the cells lining the bladder. Patients enrolled in the trial suffered from an advanced form of the cancer despite undergoing chemotherapy.
Keytruda, which belongs to a new class of medicines called PD-1 inhibitors that help the immune system unmask hidden cancer cells, generated second-quarter sales of $314 million.
The drug, along with rival Bristol-Myers Squibb & Co's Opdivo, is already approved to treat a common form of lung cancer.
Analysts expect that the treatments will rake in tens of billions of dollars in sales in the years ahead, as they are tested for other types of cancer.
A newer entrant to the immunotherapy space is Roche Holding AG, whose drug Tecentriq won U.S. approval in May for bladder cancer, followed by lung cancer this week.
I agree TJ, that's why I mentioned earlier that following the data I think we're going to see the analysts revise their coverage upward significantly – – once they get the new timelines, amendments, and new device and molecule announced.
RE: I&A Day, New "Go-Anywhere" electroporating catheter, New Molecule prepping for P1 trial, Amending Protocol for next 6mths of P2B Combo trial, Fast Track and registration timelines. I don't know, maybe it's just me, but I'd say they have some updating to.
First, to the science community at SITC; then secondly, the professional community. I personally like the idea that Investors and Analysts alike would be given a more personal and extended (2 hour) look, and will be given a more inclusive set of information upon which to more properly assess PPS value for 12 months and to woo intitutional investoers.
I think they will release better than good news--since they are so quickly ready to share released data. Then let that bake into the PPS awhile. And by summer to a fund raising campaign.
I was actually thinking that Amending the present trial might we can figure this is a registration fast track direction.
Hello Titan, if you don't mind I'll give you my thoughts. The analyst of gotten wrong wrong for the past four years and McCarthy has a 38% success with his guesses. No offense to their professionalism but I could flip a coin and do better than them. Their analysis is slow and behind the curve when it comes to the technological advancements in immunotherapy. They keep a conservative viewpoint for their investors to cover their liability – – Pack they completely missed the bio tech bubble collapsing… That's why they have lowered their price expectations for OncoSec. This company with good results should place them in a multibillion-dollar context for either purchase or licensing. If the data is mediocre I'm getting the hell out of Dodge, but if they come through like a believe they will I think it's going to exceed many peoples hopes.
It's important to remember what OncoSec is up against.
PHASE I: Approximately 70% of drugs move to the next phase
PHASE II: Approximately 33% of those drugs move to the next phase
PHASE III: Approximately 25-30% of drugs move to the next phase
That means out of every 1000 drugs in development only 57 out of a 1000 make it. This upcoming PHASE IIB interim data is very important with these kind of odds. I still would prefer a buyout and let Big Pharma assume the risk of further development.
The Sunrise platform of Peregrine, having it's own safety profile, would be required by FDA standards to initiate PII clinicals, a step backward for ONCS since they are ready to reveal it new complex molecule before first of the year. I also think Oncosec, with its ability to accurately determine responsiveness to PD-1 Keytrudy is already on the road to superior results and "Sunrise" would simply gum up the works.
What your proposing is to take a combination trial that is potentially amending it's protocol to facilitate not only a registration trial but possibly on a "Fast Track" status, in introduce a New product that has no mouse trials testing for safety and efficacy (like IL-12 and Pembrolizamab do would be a big no no to the FDA.
In fact, Sunrise simply shows how far out in front OncoSec is in Combination with a PD-1 in that respect. Not to mention the importance of Keytruday being the PD-1 be combined with (see the article posted, "BRISTOL WAITS FOR THE OTHER PD-1 SHOE TO DROP"). Not all PD-1's are created equal and Keytruda is sifting to the surface and proving it's superiority and ImmunoPulse, Like a barnacle on a whale's belly, is going to go right along with it I believe.
Me neither
Thanks TJ, I've been so fixated on the phase 2B data I completely forgot about anything else popping up before then.
Ya know HC, there are few on this board where that statement would mean something to me, and you are definitely one of them )
I gotta say, about the last Half an hour of trading today– – doesn't quite look like institutional buying, but what do I know. It seems more like retail investors trying to get something going long before the going is ready to get going. We need a hard data to be driving this thing realistically-- everybody knows it and no one's going to be fooled by hype.
Just as an aside, I'm guessing you are either military or X military or European judging by the way you use the 24 hour time clock. Am I right?
Hey there HC, it's nearly 3 to 1 buying overselling – – there's definitely a lot of buying going on.
BRISTOL WAITS FOR THE OTHER PD-1 SHOE TO DROP
Fri, 10/14/2016 - 14:41 EDT - Seeking Alpha
Bristol-Myers Squibb (NYSE:BMY) has already been hammered twice this year on disappointments over Opdivo’s potential in lung cancer, the latest setback seeing its market cap lose $10bn over the Esmo weekend. Now it faces the prospect of being squeezed in the second-line setting, where Roche’s (OTCQX:RHHBY) Tecentriq is likely to be approved next week.
Tecentriq is backed by unexpectedly strong data from the Oak trial. Even though Opdivo still retains the advantage of being eligible to treat all-comers second line, the monumental failure of its Checkmate-026 trial suggests that in the long run a gap is opening up that Bristol will struggle to close.
The sellside is fast cottoning on. In a note from Bernstein today Tim Anderson writes that it might no longer be correct to assume that Opdivo will outsell Merck & Co’s (NYSE:MRK) Keytruda in the long term – even though this is precisely what consensus, and Bernstein itself, still models.
The assault has come quickly and from a several sides. While this year consensus, as compiled by EvaluatePharma, still sees Opdivo outselling Keytruda by $4.7bn versus $1.3bn, the Merck agent beats Opdivo hands down in the number of studies initiated, which Jefferies reckons could result in almost twice as many approved indications versus Opdivo.
Much of this is based on an in-depth analysis of ongoing clinical trials by The Cancer Letter, the upshot of which is that there are now 20 anti-PD-1/PD-L1 agents in the clinic, in a combined 803 trials seeking to enrol 166,736 patients. Moreover, Keytruda is being tested in 337 trials, versus just 222 for Opdivo.
A similar analysis by EP Vantage last year looked at the burgeoning number of immuno-oncology combination studies ongoing, and the conclusion that this area has become hugely competitive – and perhaps that pharma has staked too much cash on the same horse – is unavoidable.
Pincer movement
Against this pressure Opdivo now looks to be attacked in a pincer movement from Tecentriq in relapsed patients and Keytruda first line – Opdivo’s potential in first-line NSCLC has evaporated as the Esmo presentation showed Checkmate-026 to be even worse than expected, with no benefit for Opdivo even in >50% PD-L1 expressers.
I'm figuring FDA--the present investigator sponsored trial was organized through them with the goal of reach FDA standards for Accelerated Approval (Accelerated Approval most benefits drugs pursuing long-term clinical outcomes with predictive intermediate endpoints where patients cannot afford to wait through lengthy pre-approval trials--like people dying of level III/IV melanoma).
Accelerated Approval impacts clinical trial design and post-market planning, so OncoSec would be generally advised to discuss it with FDA during trial development and advancement.
I'm curious if ImmunoPulse/Keytruda could, under an amended protocal, could qualify for "Fast Track" design.
I transcribed some of the Q&A I found interesting for our purposes here.
Rodman and Renshaw put forward a question asking whether the interim data will be based on the first 15 patients? Sharron Garosky responded saying that it will be data based on 15 patients who have received 12 weeks of treatment and in some cases much more and will be presenting the primary endpoints for that data set. Rodman and Renshaw then continued by asking clarification about completing enrollment of 42 patients by the end of this calendar year. Garosky's response is very interesting. She said, "That was our intent, um, I've been very excited by the daaata (she says with a happy gasp)we've seen in our first 50% of the patients that we have first enrolled right now and we are now actually in discussions about amending this protocol such that we can extract even more data to fulfill that unmet medical need of PD-1 progressing patients and how we can benefit with the combination therapy, so that's currently in discussions."
Rodman and Renshaw then continues by wondering "if the interim data is really positive, it is possible that the rest of the study could be modified to become a pivotal trial?" Sharon responded by saying, "it couldn't be pivotal ( meaning the type of clinical trial intended to provide evidence for FDA marketing approval. Pivotal phase 2 trials are extremely rare), because that's not the way the study was designed. It is an IST ( investigator sponsored trial) sponsored study with OncoSec. We would still go forward with our own classic study which would be supported in our BLA ( biologic license application ) Filing. That's why our study of our own patients coming into the trial, who are actually progressing on the PD-1 therapy and then we give them the combination to try and rescue and get those patients into remission, either partial or complete, is the focus we need to make and this data of the interim that we are presenting is very supportive of that. But that first group of patients is only biochemically defined as the nonresponders and we would like to amend that protocol to to look at patients that are progressing and extract those, but it's not going to be powered and significant enough to be able to do our full study, which we are planning to present and take to the agency."
Rodman and Ranshaw asks a final question of, When do you expect to have data from the 42 patients?"
PD answers this one by saying, "we will have the full data from the current ongoing study in 2017, at this moment we're focusing on discussing the interim data results and then we will follow with the full data package as all these patients are mature in the beginning part of next year or first half of next year."
PD declined to talk about any registration trial aspects until after the interim data has been presented at the SITC conference and then lay out the full registration development plan. And we are planning to have an analyst and investor day on November 17, 2016, where the focus of the discussion will be on the entire registration and developmental plan for melanoma.
From the Q&A, it was discussed when final data would be released for the combination clinical trial phase to be when Sharon Grosky said we might not even complete the same protocol we're on because the results are so good ( paraphrase )
Pierce gone!?! Ha Ha, "Biomarkers and Precision Medicine USA Congress
In addition, Robert Pierce, MD, Chief Scientific Strategist and Adil Daud, MD, Chief Clinical Strategist at OncoSec, were both invited as speakers and presenters for the Annual Biomarkers & Precision Medicine USA Congress that was held in San Diego, CA from October 3-4, 2016."
When Pierce was interviewed just a week ago saying,
"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!"
I think this is why Dirk:
Collaborations
The Society for Immunotherapy of Cancer (SITC) recognizes that collaborations are an essential component to driving the field of cancer immunotherapy forward, and therefore seeks to expand its impact establishing relationships with like-minded organizational partners. Through these relationships, SITC creates channels of information exchange. SITC has established project-driven and long-standing collaborative relationships with numerous domestic and international organizations, including the following associations and organizations, government and regulatory agencies, patient advocacy organizations and foundations.
Associations & Organizations
Domestic
Advanced Medical Technology Association (AdvaMed)
Advancing Transfusion and Cellular Therapies Worldwide (AABB)
AIDS Clinical Trials Group (ACTG)
American Association for Cancer Research (AACR)
American Association of Immunologists (AAI)
American Cancer Society Cancer Action Network (ACS CAN)
American Society for Blood and Marrow Transplantation (ASBMT)
American Society for Radiation Oncology (ASTRO)
American Society for Cell Biology (ASCB)
American Society of Clinical Oncology (ASCO)
American Society of Gene and Cell Therapy (ASCGT)
American Society of Hematology (ASH)
American Society for Radiation Oncology (ASTRO)
Association of American Cancer Centers
Association of Northern California Oncologists (ANCO)
Association of Community Cancer Centers (ACCC)
Association of Oncology Social Workers (AOSW)
Biotechnology Industry Organization (BIO)
Cancer Immunotherapy Consortium (CIC)-Cancer Research Institute (CRI)
Clinical Immunology Society (CIS)
College of American Pathologists (CAP)
Commission on Cancer (CoC)
Community Oncology Alliance (COA)
Federation of Clinical Immunology Societies (FOCIS)
Foundation for the Accreditation of Cellular Therapy (FACT)
Hematology Oncology Pharmacists Association (HOPA)
International Association for the Study of Lung Cancer (IASLC)
International Society for Cellular Therapy (ISCT)
Keystone Symposia
Kidney Cancer Association (KCA)
National Coalition for Cancer Research (NCCR)
National Comprehensive Cancer Network (NCCN)
National Coalition of Oncology Nurse Navigators (NCONN)
Ohio Hematology Oncology Society (OHOS)
Oncology Specialty Group (OSG)
Tumor Vaccine and Cell Therapy Working Group (TVACT)
International
Adoptive Engineered T Cell Targeting to Activate Cancer Killing (ATTACK), France
Arab Medical Association Against Cancer (AMAAC), Egypt
Association for Immunotherapy of Cancer (CIMT), Germany
Canadian Cancer Immunotherapy Consortium (CCIC), Canada
Cancer Drug Development Forum (CDDF), Germany
Cancer Immunotherapy and Immunomonitoring (CITIM)
Center for Immune Modulatory Therapies for Autoimmunity and Cancer (IMTAC), Sweden
Chinese American Hematologist Oncologist Network (CAHON), China
Chinese Anti-Cancer Association (CACA), China
Chinese Immunotherapy and Immunomonitoring (CITIM), China
Chinese Immunotherapy Trials Network (CITN), China
Chinese Society of Clinical Oncology (CSCO), China
Chinese Society for Immunology (CSI), China
Committee for Tumor Immunology and Bio-Therapy (TIBT), China
Dutch Tumor Immunology Working Party (DTIWP), The Netherlands
European Academy of Tumor Immunology (EATI), France
European CanCer Organisation (ECCO)
European Congress of Immunology (ECI), United Kingdom
European Society of Cancer Immunology and Immunotherapy (ESCII), Greece
European Society for Medical Oncology (ESMO)
Fondazione Melanoma ONLUS, Italy
German Cancer Immunology group in the German Immunology Society (DGFI), Germany
Grupo Español de Terapias Inmuno-Biológicas en Cáncer (GÉTICA), Spain
International Society for Cellular Therapy (ISCT), Canada
Istituto Nazionale Tumori Fondazione G. Pascale, Italy
Italian Melanoma Intergroup (IMI), Italy
Italian Network for Tumor Biotherapy (NIBIT), Italy
Japanese Association of Cancer Immunotherapy (JACI), Japan
National Institute of Oncology, Budapest, Hungary
Progress in Vaccination Against Cancer (PIVAC), Europe
Royal Society of London, England
Scandinavian Network for Immunotherapy of Cancer (SNIC), Scandinavia
Sidra Medical and Research Center, Qatar
Swiss Institute for Experimental Cancer Research (ISREC), Switzerland
Tumor Immunology Meets Oncology (TIMO)
Government & Regulatory Agencies
Domestic
Cancer Immunotherapy Trials Network (CITN)
Cancer Moonshot Blue Ribbon Panel
Cancer Therapy Evaluation Program (CTEP)
Food and Drug Administration (FDA)
National Cancer Institute (NCI)
National Heart, Lung and Blood Institute (NHLBI)
National Institutes of Health (NIH)
Production Assistance for Cellular Therapy (PACT)
International
Center for Drug Evaluation, (SFDA), P.R. China
Department of Biotechnology (DBT), Government of India
European Medicines Agency (EMEA), United Kingdom
Health Canada, Canada
Japan Science and Technology Agency (JST), Japan
Paul-Ehrlich-Institut (PEI), Germany
Pharmaceuticals and Medical Devices Agency (PMDA), Japan
State Food and Drug Administration (SFDA), P.R. China
Swissmedic, Swiss Agency for Therapeutic Products, Switzerland
Patient Advocacy Organizations & Foundations
AIM at Melanoma
Bonnie J. Addario Lung Cancer Foundation
Cancer Support Community (CSC)
Cancer Research Institute (CRI)
Friends of Cancer Research Foundation
Gilda’s Club
Global Resource for Advancing Cancer Education (GRACE)
Immuno-Oncology Policy Working Group
LUNGevity
Lung Cancer Alliance (LCA)
Melanoma Foundation
Melanoma Research Alliance (MRA)
Melanoma Research Foundation (MRF)
Patient Active in Research (PAIR)
Prostate Cancer Foundation (PCF)
Research Advocacy Network (RAN)
Research!America
Skin of Steel
Solving Kids’ Cancer
Stand Up To Cancer (SU2C)
About the SITC Annual Meeting
The Society for Immunotherapy of Cancer (SITC) is a non-profit medical professional society of influential scientists, academicians, researchers, clinicians, government representatives, and industry leaders from around the world dedicated to improving cancer patient outcomes by advancing the science and application of cancer immunotherapy. Currently, SITC has nearly 1,600 members representing 17 medical specialties and are engaged in research and treatment of at least a dozen types of cancer.
Date and Time: November 11, 2016 at 12:15 pm EDT (Oral poster presentation to be defined)
Location: Prince George's Exhibition Hall AB, Gaylord National Resort & Convention Center
Thanks Dirk, I missed that.
Hey Twiz, why do you think that?
I agree TJ, I have watch chart pattern be violated on a consistant basis. Primarily due to low volume of retail investors and apathy that is now present as everyone knows we have to have data! This has been burned into those investors and traders here from the days of hype, PR's, delayed trials, and most importantly the shift in science from monotheraphy to need for proof of combotherapy, And most importantly--this science of turning Non-responders into responders is the first of its kind--there needs to be real news to move this thing...with a big pop or strong, consistant build in volume, either way, you don't want to be on the sidelines for any of these conferences with the PPS at rock bottom levels.
Why would you?
Jan-Sept.--14 conferences; Oct.-Dec.--24 confs.
It's always good for business's to expose it's self--especially on the international stage. Products often find a speedier route to registration do to less regulation on the European stage. Japan as well.
The question I would like to consider is...why the dramatic increase in quality/prominent conferences/meetings (Nearly doubling the prior 9 months worth of conferences within a three month period?
Ego? Luxury vacations? Like to act like big shots? Tax right-off? Punit just hates to be with his wife and children? They are board just sittin' around in the office during the winter months (although San Diego, CA average temp. Oct thru Dec. is 70 degrees),
Maybe OncoSec's World Class Scientists like Daud and Pierce and staff like to stand up on the world stage showing off just what materialistic embezzlers and frauds they really are while suck the last life's blood $$$$ out of the company---clinking champagne glass's and laughing at all the idiot patients who gave up the few remaining weeks of their diseased lives for a business that exists just line their greedy little pockets.
Or maybe, JUST maybe, OncoSec has something they believe in and that it is actually saving lives (I vote for this one--but that's just me). I'm going with what Pierce recently said in an interview,
"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!