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Thanks for your insights kmastra. I agree it's a high risk investment. Hence only holding a small position at this time.
Thanks rogerm for your insights. One of the main reasons for my interest in MRNS is the big institutional buys in the last couple of months before the p2 data evaluating children with CDKL5 disorder due this quarter. Will only be maintaining a small position. Cheers.
MRNS - Anyone have any thoughts on this vs. SAGE, or anything in general about MRNS? Thanks in advance.
IL-12 Up-Regulates CD40 Ligand (CD154) Expression on Human T Cells1
http://www.jimmunol.org/content/jimmunol/160/3/1166.full.pdf
Unrelated to ONCS. Just regarding IL-12.
Newsletter
http://oncosec.com/oncosec-quarterly-update-august-2017/
Looks like it will take some time to get the trial started.
Congratulations Dew!
There may be TNBC p1 data, or additional p2b data from the existing UCSF trial, or some TAP announcements, all of which I think will be immaterial to impact the share price. That 2017 licensing milestone, although it now says "evaluate" at the beginning, may result in a slight lift if it does happen and if the collaboration is with a big pharma. I don't think it will be a $ deal. Perhaps another drug supply agreement.
All eyes will be on registration trial interim data in late Q4 (assuming some sites have already begun recruitment) or Q1'18 IMO.
The former Lucky Strike maker is spending billions on 'next-gen nicotine delivery systems'
http://read.bi/2pENZkq
'Where’s the next disruptive technology going to come from?'
Innovation in Big Tobacco is also bringing companies like BAT into contact with the startup world. BAT has made several acquisitions in the vaping and e-cigarette space since the turn of the decade.
"I’ve got a whole function here purely based on disruptive technology," Dr. O'Reilly explains. "It’s about 30 in that group, dedicated to what we call new consumer technology platform.
"They’re just looking out there, where’s the next disruptive technology going to come from? And when they identify them, we can look to work with them, acquire them, develop the technology. We become the disruptors."
Tiny Biotech's Tobacco Tinkering Makes It a Rare Winner
https://www.bloomberg.com/news/articles/2017-08-04/tiny-biotech-s-tobacco-tinkering-makes-it-smoking-s-rare-winner
My take on the delay in trial announcement is that it could be because of the number of trial sites this time, 20+, vs. only 2 sites for last trial. They may be waiting to get these sites all ready before updating clinicaltrials.gov and issuing a press release. Just a guess.
Biotechnology: the US-China dispute over genetic data
https://www.ft.com/content/245a7c60-6880-11e7-9a66-93fb352ba1fe
- The FBI is beginning to raise national security questions about genetic data going overseas
Biotechnology: the US-China dispute over genetic data
https://www.ft.com/content/245a7c60-6880-11e7-9a66-93fb352ba1fe
- The FBI is beginning to raise national security questions about genetic data going overseas
It looks like Amazon would be losing a lot of money if not for AWS
https://techcrunch.com/2017/07/27/it-looks-like-amazon-would-be-losing-a-lot-of-money-if-not-for-aws/
XXII +22% on FDA guidance for tobacco companies to reduce nicotine to non-addictive levels
Tobacco stocks plunge as FDA eyes nicotine clampdown
http://nyp.st/2v6A1xX
A humbling setback for an immune-revving cancer therapy underscores the many questions facing the field
- by AF
https://www.statnews.com/2017/07/27/immunotherapy-cancer-questions/
Key partner cuts ties with brash biotech startup Moderna, raising big questions about its pipeline
https://www.statnews.com/2017/07/27/moderna-alexion-partnership/
Moderna has been facing some setbacks in recent months. Can ONCS/MighTy succeed in their similar objective to manufacture MABs within patients' bodies using DNA (Moderna is trying to do the same using RNA)?
Key partner cuts ties with brash biotech startup Moderna, raising big questions about its pipeline
https://www.statnews.com/2017/07/27/moderna-alexion-partnership/
Checkpoint Inhibitors Moving Ahead in Breast Cancer
https://shar.es/1TCGrj
Checkpoint inhibitors against PD-1 and PD-L1 have demonstrated promising efficacy as monotherapies and in combination with chemotherapy for patients with triple-negative breast cancer (TNBC), with phase III data on the horizon, according to a presentation by Sylvia Adams, MD, at the 16th Annual International Congress on the Future of Breast Cancer East.
"We think there is definitely value for immune checkpoint blockade in triple-negative disease. When you look at the metastatic trials, while the response rates are relatively low, most of the responses are durable," said Adams, from the NYU Langone Medical Center. "For patient selection, it is important to consider the line of therapy. The earlier the better."
Response to PD-1 or PD-L1 inhibition is frequently associated with the presence of tumor infiltrating lymphocytes (TILs). In breast cancer, PD-L1 expression is almost exclusively seen on TILs and not the tumor cells. As a result, PD-L1 expression is highest in patients with TNBC, inflammatory breast cancer, and ductal carcinoma in situ. At this point, the most promising results have been observed in the TNBC population, with early findings showing promise in the neoadjuvant space.
Single-Agent Activity
A handful of early phase studies have reported findings for the PD-1 inhibitor pembrolizumab (Keytruda) and the PD-L1 inhibitor atezolizumab (Tecentriq). These agents have shown durable responses, with higher rates seen in the earlier settings for those with metastatic TNBC.
Atezolizumab monotherapy was explored in a phase I study for those with metastatic TNBC in the frontline or pretreated setting.1 The objective response rate (ORR) for those in the frontline setting (n = 19) was 26%. In the second-line group (n = 28), the ORR was 4% and in the third-line and beyond (n = 65) the ORR was 8%.
In this study, which had the longest follow-up for a study of a checkpoint inhibitor in breast cancer, the 1- and 2-year overall survival (OS) rates in the frontline setting were 63% and 47%, respectively. For those who received 2 or more lines of prior therapy, OS rates were 37% and 18%, respectively.
In the phase II KEYNOTE-086 trial,2,3 pembrolizumab at 200 mg every 3 weeks was explored in patients with metastatic TNBC as a first-line therapy in cohort B (n = 52) and heavily pretreated patients in cohort A (n = 170). Sixty percent of patients had PD-L1–positive tumors in cohort A and all patients tested positive in the cohort B.
In cohort A of the study,2 ORR was 4.7% (95% CI, 2.3%-9.2%) with single-agent pembrolizumab, including a complete response (CR) rate of 0.6%. PD-L1 status was not associated with response, with ORRs of 4.8% and 4.7% in the PD-L1–positive and –negative groups, respectively.
In cohort B of the study,3 the ORR was 23%, with a CR rate of 4%. The 3-month progression-free survival (PFS) rate was 41% and the 6-month rate was 28%. The median PFS was 2.1 months (95% CI, 2.0-3.9).
Combinations Show Strong Results
Building upon the monotherapy results, studies are now looking at the checkpoint inhibitors in combination with chemotherapy. There is preclinical evidence suggesting synergy between chemotherapy and immunotherapy, Adams noted, with other combination potentials on the horizon.
"It will be the future of breast cancer to combine immunotherapy with other targeted therapies, radiation therapy, and other agents," she added. "One of the unanswered questions is which is the best combination partner. Some of the chemotherapies are more immunogenic than others."
A phase Ib/II study explored pembrolizumab plus eribulin (Halaven) for patients with metastatic TNBC.4 Half of enrolled patients had not received prior chemotherapy and 43.6% were PD-L1–positive. In 39 evaluable patients at an interim analysis of the study, the ORR with the combination was 33.3% (95% CI, 19.5%-48.1%). The CR rate was 2.6% and 28.2% of patients had stable disease for ≥8 weeks, of which 7.7% was for ≥24 weeks.
The phase III KEYNOTE-355 study is currently exploring the safety and efficacy of pembrolizumab plus chemotherapy as a first-line therapy for patients with locally recurrent inoperable or metastatic TNBC. The trial plans to enroll 858 patients (NCT02819518).
In a phase Ib trial,5 upfront treatment with atezolizumab plus nab-paclitaxel (Abraxane) showed a confirmed ORR of 46% in patients with metastatic TNBC (n = 13; 95% CI, 19-75). The complete response in the frontline setting was 8%. Across all lines of treatment (n = 32), the ORR was 38%, with a CR rate of 3%. The PFS and OS data were not yet mature.
Following on these results, the phase III IMpassion130 study randomized 900 patients with untreated metastatic TNBC to atezolizumab plus nab-paclitaxel or placebo plus nab-paclitaxel. The coprimary endpoints of the study are PFS and OS, and the trial reached full accrual in the first half of 2017, according to Adams (NCT02425891).
In addition to the metastatic setting, the checkpoint inhibitors have also demonstrated efficacy before surgery for those with early stage breast cancer. In the phase II I-SPY 2 trial,6 249 patients with invasive disease were adaptively randomized to receive weekly paclitaxel alone (n = 180) or in combination with pembrolizumab (n = 69) followed by doxorubicin plus cyclophosphamide for 4 cycles.
For those with HR+/HER- disease, the pathologic CR (pCR) rate with pembrolizumab was 34.2% versus 13.6% in the control arm. In the TNBC group, the pCR was 62.4% with the pembrolizumab combination and 22.3% in the control arm, representing >99.9% probability of superiority and 99.3% probability of success in a phase III study.
Rare Subtype Shows High Intrigues
While most subtypes of breast cancer express PD-L1 on TILs, metaplastic breast cancer (MPBC) frequently has the ligand directly on the tumor cells. In a study of 75 MPBC samples, 46% expressed PD-L1 on the tumor cells. In anecdotal findings, a dramatic response was observed in a patient with recurrent MPBC treated with pembrolizumab. In this experience, Adams noted, there was eradication of a large tumor mass and visceral metastases.
The DART trial is exploring anti–CTLA-4 inhibition with ipilimumab (Yervoy) in combination with nivolumab (Opdivo) across a variety of rare tumors, including MPBC, Adams noted. The study was previously linked with the MATCH trial and is currently enrolling at more than 600 sites. Given the promise seen, Adams encouraged enrolled in the study for those with MPBC (NCT02834013).
References
1. Schmid P, Cruz C, Braiteh FS, et al. Atezolizumab in metastatic triple-negative breast cancer: long-term clinical outcomes and biomarker analyses. Abstract presented at: AACR Annual Meeting 2017; April 1-5, 2017; Washington DC. Abstract 2986.
2. Adams S, Schmid P, Rugo HS, et al. Phase 2 study of pembrolizumab (pembro) monotherapy for previously treated metastatic triple-negative breast cancer (mTNBC): KEYNOTE-086 cohort A. J Clin Oncol. 2017;35 (suppl; abstr 1008).
3. Adams S, Loi S, Toppmeyer D, et al. Phase 2 study of pembrolizumab as first-line therapy for PD-L1–positive metastatic triple-negative breast cancer (mTNBC): Preliminary data from KEYNOTE-086 cohort B. J Clin Oncol. 2017;35 (suppl; abstr 1088).
4. Nanda R, Liu MC, Yau C, et al. Pembrolizumab plus standard neoadjuvant therapy for high-risk breast cancer (BC): Results from I-SPY 2. J Clin Oncol. 2017; 35 (suppl; abstr 506).
5. Tolaney S, Savulsky C, Aktan G, et al. Phase 1b/2 study to evaluate eribulin mesylate in combination with pembrolizumab in patients with metastatic triple-negative breast cancer. Presented at: 2016 San Antonio Breast Cancer Symposium; December 6-10, 2016; San Antonio, TX. Abstract P5-15-02.
6. Adams S, Diamond JR, Hamilton EP, et al. Phase Ib trial of atezolizumab in combination with nab-paclitaxel in patients with metastatic triple-negative breast cancer (mTNBC). J Clin Oncol. 2016;34 (suppl; abstr 1009).
The Startling History Behind Merck's New Cancer Blockbuster
http://www.forbes.com/sites/davidshaywitz/2017/07/26/the-startling-history-behind-mercks-new-cancer-blockbuster/#74d01266948d
hschlauch, an ATM facility allows ONCS's designated broker (Oppenheimer) to raise capital in smaller chunks at prices favorable to the stock. They aren't raising $8.2M in one go. At the market offerings allow companies to raise in smaller chunks at opportune moments without the need to issue PRs that might negatively impact share price.
http://westwickepartners.com/2013/10/is-atm-financing-the-right-option-what-you-need-to-know/
As for dilution in general, yes, this was expected and factored into my expectations. Glad they went with an ATM - notice there will be no warrants, unlike the last three years when the standard cash raises have always had warrants attached.
Even if they had raised $8.2M in one go at $1 a share, that would have added 8.2M shares to the ~21M OS. ~30M shares out heading into registration data presents a good opportunity to take some calculated risk IMO.
On a separate note, I really hope the collaboration with KH gets some traction later this year/early next year such that in an event of a potential buyout by MRK if the interim reg. trial data hits 30%+ ORR next year, the value of that IP is factored in fairly. It would suck if MRK just gets that stuff for free in a cheap valuation for current lead program in melanoma.
An ATM facility with a decent company...I guess it's not that bad. They may raise in small chunks to not depress the SP. Looking forward to Q4/Q1.
ONCOSEC MEDICAL INCORPORATED (NASDAQ:ONCS) Files An 8-K Entry into a Material Definitive Agreement
https://t.co/0xoYUBPuvo
Surrogate endpoints in oncology: when are they acceptable for regulatory and clinical decisions, and are they currently overused?
- Robert Kemp and Vinay Prasad
Abstract
Background: Surrogate outcomes are not intrinsically beneficial to patients, but are designed to be easier and faster to measure than clinically meaningful outcomes. The use of surrogates as an endpoint in clinical trials and basis for regulatory approval is common, and frequently exceeds the guidance given by regulatory bodies.
Discussion: In this article, we demonstrate that the use of surrogates in oncology is widespread and increasing. At the same time, the strength of association between the surrogates used and clinically meaningful outcomes is often unknown or weak. Attempts to validate surrogates are rarely undertaken. When this is done, validation relies on only a fraction of available data, and often concludes that the surrogate is poor. Post-marketing studies,designed to ensure drugs have meaningful benefits, are often not performed. Alternatively, if a drug fails to improve quality of life or overall survival, market authorization is rarely revoked. We suggest this reliance on surrogates, and the imprecision surrounding their acceptable use, means that numerous drugs are now approved based on small yet statistically significant increases in surrogates of questionable reliability. In turn, this means the benefits of many approved drugs are uncertain. This is an unacceptable situation for patients and professionals, as prior experience has shown that such uncertainty can be associated with significant harm.
Conclusion: The use of surrogate outcomes should be limited to situations where a surrogate has demonstrated robust ability to predict meaningful benefits, or where cases are dire, rare or with few treatment options. In both cases, surrogates must be used only when continuing studies examining hard endpoints have been fully recruited.
Keywords: Surrogate endpoints, Outcomes, Cancer, Regulation, US Food and Drug Administration (FDA)
Langer-backed Kala scores $90M IPO as it lines up a pair of NDAs
https://endpts.com/langer-backed-kala-scores-90m-ipo-as-it-lines-up-a-pair-of-ndas
Kala Pharmaceuticals has now joined the ranks of this year’s biotech IPO class, hitting the range and raising $90 million after pricing shares at $15.
Kala Pharmaceuticals has now joined the ranks of this year’s biotech IPO class, hitting the range and raising $90 million after pricing shares at $15.
That cash will now help fund the final leg of two Phase III studies for two different doses of KPI-121 and the first round of commercialization work that the biotech hopes lies ahead. Their lead drug is being studied for inflammation and pain following ocular surgery as well as the temporary relief of the signs and symptoms of dry eye disease.
Back in early 2016 MIT professor Bob Langer told me that Kala had moved through preclinical work and into late-stage testing in just three years, a major accomplishment for the company. The group, which was inspired by work done by Langer and some of his students at MIT, can now add a successful IPO as they plan an NDA before the end of this year. One of Langer’s former students, Hongming Chen, is the CSO at Kala. Mark Iwicki is CEO.
The Waltham, MA-based biotech will trade as $KALA. The biotech raised $68 million in early 2016 from Longitude Capital, OrbiMed, Vivo Capital, CAM Capital, RA Capital Management, Wellington Management Company LLP, Polaris Partners, and Lux Capital.
J.P. Morgan, BofA Merrill Lynch and Wells Fargo Securities are acting as joint bookrunners for the offering. Wedbush PacGrow is acting as a co-manager for the offering.
I have lowered my expectations for that milestone as they have inserted the word "evaluate" in that milestone in the latest presentation. I think it's all going to hinge on registration trial data. Even if we are to have a different big pharma collaboration before that, it would probably only be a drug supply arrangement. What I do want to see is some traction on collaboration with MighTy Biopharma.
Please see tweet for table of response rates and hazard ratios for overall survival and progression free survival
for the two drugs
https://twitter.com/vinayprasad82/status/887322182858162179
I think trial start PR is due any day followed by a cash raise soon (perhaps the last one they do as an independent company). Then it will all hinge on interim data from the registration trial, which I expect at ASCO-SITC in Feb 2018 at the earliest. Potentially big inflection if the data can speak for itself. GLTA.
The myth of drug expiration dates
http://www.cnbc.com/2017/07/18/the-myth-of-drug-expiration-dates.html
Nivolumab and Pembrolizumab: Monoclonal Antibodies Against Programmed Cell Death-1 (PD-1) that are Interchangeable
http://www.seminoncol.org/article/S0093-7754(17)30062-3/fulltext
Nivolumab (Opdivo®, Bristol Meyer Squibb) and pembrolizumab (Keytruda®, Merck) are the first two FDA approved monoclonal antibodies targeting programmed death-1 (PD-1). Nivolumab and pembrolizumab work by interfering with the interaction between (PD-1) and programmed death-ligand-1 (PD-L1), whose unimpeded interaction downregulates T-cells allowing cancer cells to evade immune surveillance.1-3 [Figure 1] These drugs have earned a series of US Food and Drug Administration US FDA) approvals for melanoma, non-small cell lung cancer (NSCLC), head and neck squamous cell cancer (HNSCC), urothelial cancer, classical Hodgkin’s lymphoma, and renal cell cancer. In this review we will summarize the data for efficacy and toxicity for these two agents. We will conclude they represent two valuable but interchangeable alternatives to target their approved indications. We will discuss how this can help global payers seeking to contain the cost of cancer therapeutics that continues to spiral out of control.
[OT] 20 million bacteria-infected mosquitoes are getting released into a California city by a division of Google's parent company
http://www.businessinsider.com/wolbachia-mosquitoes-california-google-alphabet-2017-7
... The mosquitoes were raised by a robot that can produce a million mosquitoes a week. They're all male, so they won't bite anyone - only female mosquitoes bite humans.
The bugs have been specially raised to carry a bacteria called Wolbachia, which has an insidious effect on the reproductive process. Mosquitoes that carry Wolbachia can fly around normally and mate with females, but the eggs those females lay aren't able to hatch - unless the females are infected with the same strain of the bacteria as well.
Setting loose hoards of males carrying the bacteria, then, is like waging biological warfare on mosquitoes.
Wolbachia is common in nature, and scientists have known since 1967 that the bacteria can make certain mosquitoes and other insects sterile. Researchers working to fight mosquito-borne diseases have long been interested in using the bacteria to kill off local mosquito populations, but it wasn't until this year that they discovered how genes in the bacteria cause mosquitoes to produce nonviable eggs.
The ability to kill entire mosquito populations could significantly curb disease transmission. Mosquitoes carry diseases like yellow fever, malaria, dengue, Zika, and chikungunya, among others. They're responsible for more than 800,000 human deaths a year, making them the most dangerous animal on the planet. And in a warming world, the range of some of these disease spreaders is expanding, making population control efforts more urgent than ever.
[OT] Who Needs Hard Drives? Scientists Store Film Clip in DNA
https://nyti.ms/2u9UTEp
Millennials don’t like motorcycles and that’s killing Harley’s sales
http://www.cnbc.com/2017/07/12/millennials-dont-like-motorcycles-and-thats-killing-harleys-sales.html
Sanofi to buy Protein Sciences for $650M
http://www.reuters.com/article/us-protein-sciences-m-a-sanofi-fr-idUSKBN19W0CP
Cellectis announces proposed IPO for $100M at $15-18 a share
http://www.businesswire.com/news/home/20170710005639/en/Cellectis-Calyxt-Announces-Proposed-Initial-Public-Offering
Immunology, one cell at a time
http://www.nature.com/news/immunology-one-cell-at-a-time-1.22232
Blockchain — The New Technology of Trust
http://www.goldmansachs.com/our-thinking/pages/blockchain/
Fears over a medical gold rush in cancer drug race
Fears over a medical gold rush in cancer drug race https://t.co/ysFMrmGk76
— Financial Times (@FinancialTimes) July 2, 2017
"Keytruda in lung cancer may not be as good as we think - due to censoring"
Keytruda in lung ca - maybe not as good as we think - due to censoring. My piece with @VinayPrasad82 & @usama_bilal https://t.co/7DWrNE3rpw pic.twitter.com/zENx7n2Wa6
— Daniel Goldstein MD (@drdgoldstein) July 2, 2017
Re: Registration trial sites
Per ONCS, they have planned about 20 sites for this trial, which could be extended up to 30. The UCSF IST had only 2 sites (in CA and UT per clinicaltrials.gov). I expect the upcoming recruitment to be a lot faster than the previous IST as a result. I would expect interim data at ASCO-SITC in February or at AACR in April 2018.