Merck and ONCS to Collaborate in Phase 2b

You also have to like this bit:

"This Phase II clinical trial will be conducted as a multicenter Investigator Sponsored Trial (IST), with UCSF and Dr. Alain Algazi as the sponsor. Merck will supply pembrolizumab, and OncoSec will provide electroporation devices and plasmid IL-12."

AKA: ONCS and Merck provide the goods, and UCSF funds the trial.

Dhillon just posted a blog:


punitdhillon.com/2014/11/25/oncosec-ucsf-and-merck-initiate-a-landmark-phase-iib-combination-trial-of-breakthrough-drug-keytruda-and-immunopulse-to-treat-metastatic-melanoma/

OncoSec, UCSF, and Merck Initiate a Landmark Phase IIb Combination Trial of Breakthrough Drug KEYTRUDA® And ImmunoPulse to Treat Metastatic Melanoma
OncoSec Medical is changing the cancer experience. Today changes the course of OncoSec as we announced a collaboration with the University of California San Francisco (UCSF), to evaluate the safety, tolerability and efficacy of the combination of Merck’s anti-PD-1 drug, KEYTRUDA® (pembrolizumab), and OncoSec’s ImmunoPulse therapy (intratumoral IL- 12), in a phase II metastatic melanoma study with patients non-responsive to KEYTRUDA®. This is an Investigator Sponsored Trial led by renowned Oncologist Dr. Alain Algazi at the prestigious University of California San Francisco and supported by OncoSec Medical and Merck Research Labs. This powerful combination is expected to treat the larger population of approximately 70% of the patients for which it is not currently effective by one of the most exciting breakthrough drugs in treatment of cancer.

For the last year, OncoSec has been focused on the the tremendous unmet medical need of metastatic melanoma patients, who don’t respond to PD-1/PDL1 therapeutics. Unfortunately, these patients represent approximately 70% of metastatic melanoma patients. OncoSec data – both preclinical and clinical – demonstrates that intratumoral Immunopulse therapy with IL–12 drives an increase in TILs. Based on these data, we have proposed that Immunpulse IL-12 will “convert” anti-PD-1 non-responders into responders, leading to potentially enhanced clinical efficacy of PD-1. The field of immunotherapy is beginning to focus on where we’ve been for the last year – an awareness that PD-1 non-responders constitute a tremendous unmet medical need and business opportunity.

This collaboration is significant because of the speed of being able to get into a clinical trial to test our hypothesis and as a critical and positive step in the development of IL-12 immunotherapy. I believe this is yet another sign giving validation of the value of intratumoral immunotherapy and combinatorial approaches as part of an overall therapeutic regimen to treat cancer.

Key Highlights:

Only minority of patients respond to KEYTRUDA®
Patients who do not respond to KEYTRUDA® do not have immune cells (i.e. the correct TILs) already present in the tumor
ImmunoPulse has the potential to bring the correct immune cells into the tumor
Thus, ImmunoPulse has the potential to address the approximately 70% of patients who do not respond to KEYTRUDA®
ImmunoPulse, uses plasmid DNA that encodes for IL-12 and delivers it directly into the tumor using a proprietary delivery device. Preclinical and clinical data suggest that local delivery and expression of IL-12 with ImmunoPulse promotes tumor immunogenicity and increases tumor-infiltrating lymphocytes (TILs). Over 70 patients have been treated with ImmunoPulse, and no serious drug related toxicities have been reported to-date, which demonstrates the strong safety profile of this therapy.

ImmunoPulse has the potential to be the ultimate combination therapy with a new class of immunotherapies called, checkpoint inhibitors. Merck’s recently approved KEYTRUDA® (pembrolizumab), is the first anti-PD-1 (programmed death receptor-1) checkpoint therapy approved in the United States for metastatic melanoma, based on strong Phase 2 data, that showed a 24 percent overall response rate. Despite the deserved excitement, there still remains an unmet medical need for the approximately 70 percent of patients who do not respond to this drug. New data suggest that 24% of the Melanoma patients who best respond to KEYTRUDA® are those who already have immune cells (i.e. TILs) in the tumor, and the approximately 70 percent of the patients that have little or no immune cells in the tumor do not respond to KEYTRUDA®. Since IL- 12 promotes tumor immunogenicity and increases the number of TILs in the tumor, the combination of our therapy to increase TILs in the tumor, and KEYTRUDA® which activates these cells to kill the tumor, present an exciting landmark study to address the vast majority of the metastatic melanoma patients, as well as, have profound implications on many other tumor indications.

Dr. Alain Algazi, Principal Investigator at UCSF said, “Merck’s PD-1 antibody, KEYTRUDA®, takes the brakes off of the anti-melanoma immune responses. ImmunoPulse with IL-12 has the potential to bring immune cells and signals into the tumor so that, when KEYTRUDA® takes the brakes off the immune response, the results could be devastating for the tumor and great for our patients, allowing us to potentially use this combination approach to address a much larger population of patients with aggressive cancer then with KEYTRUDA® alone.”

Dr. Robert Pierce, Chief Scientific Officer, stated, “There is a strong rationale for combining a treatment like ImmunoPulse, which increases TILs, with a T cell checkpoint therapy like KEYTRUDA, to improve anti-tumor efficacy in low-TIL melanoma patients, which make up approximately 70% of the metastatic melanoma patients”

“We are excited and proud to announce this collaboration with Dr. Algazi and UCSF with support from Merck. The achievement of this milestone marks the first clinical trial to evaluate the combination of an anti-PD-1 antibody with an intratumoral therapy using electroporation,” commented Punit Dhillon, President and CEO of OncoSec. “Over the course of the last year, OncoSec has continually stated the need to evaluate intratumoral therapies that have the ability to convert the anti-PD-1 non-responder population to responders. We believe the combination of OncoSec’s ImmunoPulse and checkpoint inhibitors holds significant promise for the treatment of melanoma and other cancers. The caner immunotherapy market is expected to expand up to $35 billion in the next 10 years. Intralesional therapies have the potential to gain a significant portion of this market share.”

This Phase II clinical trial will be conducted as a multicenter Investigator Sponsored Trial (IST), with UCSF and Dr. Alain Algazi as the sponsor. Merck will supply pembrolizumab, and OncoSec will provide electroporation devices and plasmid IL-12. Enrollment is expected to begin in Q1 2015.

About Checkpoint Inhibitors and Combination Approaches

Checkpoint inhibitors have shown promise in a hard-to-treat cancer such as metastatic melanoma. The objective response rate (ORR) with checkpoint inhibitors, like Yervoy (anti-CTLA-4) or Keytruda (anti-PD-1), is in the 10-40% range. There is an obvious need to improve responses and address the needs of the remaining melanoma patients who do not respond to these therapies, thus interventions that complement checkpoint inhibitors are needed.

Mechanistically, checkpoint inhibitors allow the immune cells to recognize and kill the tumors, however, if there are no immune cells already present in the tumor then these checkpoint inhibitors may not be effective. Therefore checkpoint inhibitors may be helped by combining with agents that enhance the infiltration of immune cells into the tumor. It is widely believed and demonstrated in pre-clinical studies (and maybe in early clinical studies) that combining checkpoint inhibitors with complementary immune therapies that can engage a broader immune response could lead to increased efficacy. Of equal importance, is to find potential combination therapies that not only have the potential to improve efficacy, but also pose minimal risk in increasing potential immune- related toxicities.

About KEYTRUDA®

KEYTRUDA is a human programmed death receptor-1 (PD-1)-blocking antibody indicated for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. This indication is approved under accelerated approval based on tumor response rate and durability of response. An improvement in survival or disease-related symptoms has not yet been established.

About metastatic melanoma

Skin cancer is one of the most common types of cancers diagnosed in the United States, with an estimated 2 million new cases annually. Melanoma is the most deadly type of skin cancer, leading to 75% of all skin cancer related deaths due to systemic metastatic spread. Of the 76,000 new Melanoma diagnoses estimated to occur in 2014, approximately 12% will have progressed to stage III or IV melanoma already with a 5- year survival rate of only 15%. Even today, treatment options for melanoma remain limited.

Alain Algazi, M.D. Melanoma Specialist

Dr. Alain Algazi, an oncologist, is a skin cancer specialist in the Melanoma Center at the UCSF Helen Diller Family Comprehensive Cancer Center. He treats patients with high- risk and advanced melanoma as well as those with extensive squamous cell and merkel cell carcinoma of the skin. These trials give patients access to new medications, including drugs called BRAF inhibitors that cause melanoma tumors to shrink in a majority of patients treated. He is looking for ways to improve the effectiveness of these medications.

Algazi earned a medical degree at the UCLA School of Medicine and completed an internal medicine residency at UCLA Medical Center. He completed a fellowship in hematology and oncology at UCSF. He is a member of the American Society of Clinical Oncology and American Association for Cancer Research. He is a clinical instructor at UCSF.

About Merck

Merck & Co., Inc. provides various health solutions through its prescription medicines, vaccines, biologic therapies, animal health, and consumer care products worldwide. The companys Pharmaceutical segment offers human health pharmaceutical products, such as therapeutic and preventive agents for the treatment of human disorders in the areas of cardiovascular, diabetes and obesity, respiratory, women’s health and endocrine, inflammatory and infectious diseases, oncology, ophthalmology, immunology, infectious diseases, and others. This segment also provides vaccines, including preventive pediatric, adolescent, and adult vaccines. Its Animal Health segment discovers, develops, manufactures, and markets animal health products comprising vaccines, antibiotics, and anti-inflammatory drugs for respiratory diseases, as well as products for the treatment of fertility disorders. The company was founded in 1891 and is headquartered in Whitehouse Station, New Jersey.

Then swoops in Zack's to save the day. They just raised their 12 month target price from $2 to $4:

finance.yahoo.com/news/oncs-results-newly-initiated-phase-140000517.html

ONCS: Results from Newly Initiated Phase II Combination Trial Could Lead to a Big License Deal
Zacks Small Cap Research By Zacks Small Cap Research
1 hour ago


By Grant Zeng, CFA

OTC:ONCS

Earlier today, OncoSec Medical (ONCS) announced the initiation of a landmark Phase II combination trial in collaboration with the UCSF and Merck to evaluate the safety, tolerability and efficacy of Merck’s anti-PD-1 drug, KEYTRUDA® (pembrolizumab) in combination with OncoSec’s ImmunoPulse therapy (intratumoral IL- 12) for the treatment of metastatic melanoma patients, who are non-responsive to KEYTRUDA®.

This Phase II clinical trial will be a multicenter investigator sponsored trial (IST), with UCSF and Dr. Alain Algazi as the sponsor. Merck will supply pembrolizumab, and OncoSec will provide electroporation devices and plasmid IL-12. Enrollment is expected to begin in 1Q15.

Immune checkpoint inhibition is the one of the most promising area for the treatment of cancer. Both CTLA-4 and PD-1/PDL-1 inhibitors have shown impressive results in clinical care and in ongoing clinical studies. Recent approval of Yervoy (CTLA-4 antibody from BMS) and Keytruda (PD-1 antibody from Merck) demonstrated the importance of immune checkpoint inhibitors in the treatment of cancer. We think the cancer immunotherapy by immune checkpoint inhibitors will enter widespread clinical use and will command a large market share of the cancer care market within the next decade.

Studies have demonstrated that tumors (specifically melanoma) can be divided into a high and low TIL (tumor infiltrating lymphocyte) phenotype. Tumors with high TIL are referred to as immunogenic, while tumors with low TIL are referred to non-immunogenic. Ongoing clinical trials of PD-1/PDL-1 inhibitors suggest that response correlates with high TIL phenotype. Tumors with low TIL have low response rate to PD-1/PDL-1 inhibitors.

Anti-PD-1 non-responders constitute the majority of patients even in “immune therapy” tractable tumors like melanoma and RCC. Recent melanoma studies have reported response rates in the range of 20-40% using anti-PD-1 or anti-PDL-1, and the argument is that the majority of the responders are the high-TIL population. If this is the case, then the question becomes how to make those non-immunogenic tumors into immunogenic tumors so that they can respond to PD-1/PDL-1 or similarly effective T cell checkpoint agents.

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Since IL- 12 promotes tumor immunogenicity and increases the number of TILs in the tumor, the combination therapeutic concept is that ImmunoPulse will convert low TIL tumors into high TIL ones, thus allowing KEYTRUDA® to kill tumor in patients, who would otherwise be PD-1 unresponsive.

This Phase II combo study presents a potential to address the vast majority of the metastatic melanoma patients, as well as, has profound implications on many other tumor indications.

The potential ability of ImmunoPulse to convert the non- or weakly immune-responsive cancer into strongly immune-responsive cancer may represent a paradigm shift in cancer therapy. This area is an enormous unmet medical need and represents a huge market for OncoSec. It is estimated that about 50% to 80% cancer patients will not have TIL infiltrate at baseline or even after PD-1/PDL-1 treatment. This is where OncoSec’s ImmunoPulse can get in and convert those non-immunogenic tumors into immunogenic tumors. In addition to melanoma, ImmunoPulse can virtually target any solid tumors, which represents a multi-billion dollar market for OncoSec.

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There is a huge unmet medical need for OncoSec’s ImmunoPulse in combination with checkpoint inhibitors. If we look at the melanoma indication alone, this is a disease that has the highest response rates with PD-1 inhibitor monotherapy. But still there are about 60% to 80% of patients who will not respond to PD-1 checkpoint inhibitors. This powerful combination is expected to treat the larger population of approximately 70% of the patients.

In other solid tumors, the percentage of PD-1 non-responders/non-immunogenic tumors is likely to be even greater. Thus, there is a tremendous unmet medical need, across many solid tumors.

We estimate the market for the combination therapy will be a multi-billion business.

The Phase II combination study will provide the Company with information for a key inflection point in the development of this program. If the Phase II study can confirm safety and efficacy of ImmunoPulse, pivotal trial could start in early 2016. And we estimate approval of ImmunoPulse for the treatment of melanoma may be obtained as early as in late 2017 if the pivotal trial data prove to be positive.

We think positive data from the Phase II combination study may lead to a major license deal for OncoSec.

We Maintain Outperform Rating and Raise Our Price Target to $4

We maintain our Outperform rating on OncoSec shares and raise our 12-month price target to $4.00 from previous $2.00 due to the clinical advancement of the combination study with the PD-1 inhibitor.

OncoSec is an emerging biotech company focused on developing and commercializing innovative approaches for the treatment of cancers. OncoSec’s key platform technology is its proprietary electroporation delivery system to locally deliver DNA or chemotherapeutics into tumor cells. But what makes the technology unique is that this locally delivered DNA has demonstrated systemic response for the treatment of melanoma, meaning that the technology can be used to treat metastasis of cancers.

OncoSec’s lead candidate ImmunoPulse is a delivery device encoding for IL-12. ImmunoPulse is currently in three Phase II clinical trials for melanoma, Merkel cell carcinoma and cutaneous T-cell lymphoma respectively. OncoSec already reported positive data from the Phase II melanoma trial.

One important application of ImmunoPulse is that it can be combined with checkpoint inhibitors such as PD-1/PDL-1 for the treatment of melanoma and other solid tumors. In this case, the combination therapy can convert non-immunogenic cancers into immunogenic cancers, which can be killed by the combination therapy. The Company already initiated a Phase II combination trial for melanoma. If data are positive from the combination study, pivotal trial for melanoma could start in early 2016, and approval of this indication could be obtained as early as in 2017.

The market for ImmunoPulse is huge even for the melanoma indication alone. If we consider other indications for solid tumors, the market is much bigger.

Based on OncoSec’s fundamentals, we think its shares are undervalued at current market price. Currently, OncoSec shares are trading at about $0.50 per share, which values the company at $122 million in market capitalization based on 244 million outstanding shares. This certainly is a huge discount compared to its peers. We understand that valuing a development stage biotech company is always difficult. But if we look at similar companies in the cancer space, the value of a typical development stage biotech firm with similar fundamentals to OncoSec is usually from $50 million to $1 billion depending on how advanced the programs are and how big the markets are for its candidates. OncoSec is a mid-stage development biotech company. The market of melanoma and/or other solid tumors is huge for its lead candidate ImmunoPulse.

With the estimated approval of ImmunoPulse in 2017, we model OncoSec will become profitable in fiscal 2018 with earnings per share (EPS) of $0.01 based on ImmunoPulse sales of $50 million. Revenue will increase to $215 million in fiscal 2020 and EPS will grow into $0.22 per share according to our estimates. We think a 45 x P/E multiple is appropriate for OncoSec. Using this P/E ratio and a 20% discount rate for five years, we arrive at our price target of $4.00 per share for OncoSec, which values the Company at $900 million in market cap. This valuation is appropriate in our view considering the relatively strong fundamentals of the Company.

Recent interest in electroporation technology from big pharma could serve as a wildcard for OncoSec valuation. In September 2013, Roche entered into collaboration with Inovio Pharmaceuticals with an over $400 million investment in Inovio’s electroporation technology. Also in Feb 2014, Pfizer entered into a collaboration agreement with Ichor Medical Systems to utilize Ichor’s intramuscular electroporation technology. With proven clinical data, OncoSec’s ImmunoPulse could be the next target for big pharma companies.

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Zack's to the rescue, lol.  On a pretty good run, maybe we'll even see $.60 today?  

I hear you.  I'll trade/sell some if we get to .70ish, but I'm planning on holding 1/2 this position long.  Take a look at what happened to Inovio's (INO) market cap after they announced the partnership with Roche for their electroporation technology.  ONCS could easily get to a $1B market cap on great Phase 2b combo results with Merck's PD-1, as it'll set the stage for deals for other indications beyond melonoma.

hop,

I generally try to avoid buying into rallies.  That said, here is a link to a recent breakdown at the Stifel conference.  Today is the 1st of 5 milestones that have been promised to be met by the end of the year.:


thebiotechinvestor.freeforums.net/post/9388/thread

Agree with buying into rallies.  As I said, going to wait a few days before buying in.  Thanks for the link.  Will do my DD...

Don't say things like that. If we get him good and pumped, JHam may start demanding a cut of our profits before he posts.

Nice prediction... on the nose.

I just read the CEO's blog and the Zack's article again.  Lots of potential here.  IMO, the technology is going to have big success turning non-responders into responders.  The fact that big pharma is starting to pour money into these promising electroporation companies (not many of them) bodes well for ONCS.