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Three EFTs to consider during a Market correction:
https://www.investopedia.com/three-leveraged-etfs-to-trade-a-stock-market-correction-4797064?utm_campaign=quote-yahoo&utm_source=yahoo&utm_medium=referral&yptr=yahoo
You can listen in by registering at this link:
Presentation Information:
Date:
Tuesday, December 10, 2019
Time:
9:20 AM PT / 12:20 PM ET
Location:
Luxe Sunset Boulevard Hotel (Los Angeles, CA)
Webcast:
http://wsw.com/webcast/ldmicro17/adxs/
Renaissance Technologies LLC lifted its position in shares of Advaxis, Inc. (NASDAQ:ADXS) by 143.7% in the 2nd quarter, according to its most recent disclosure with the SEC. The fund owned 501,000 shares of the biotechnology company’s stock after acquiring an additional 295,444 shares during the period. Renaissance Technologies LLC owned 2.91% of Advaxis worth $1,047,000 as of its most recent filing with the SEC.
Separately, JPMorgan Chase & Co. increased its holdings in Advaxis by 53,633.7% in the second quarter. JPMorgan Chase & Co. now owns 51,047 shares of the biotechnology company’s stock worth $107,000 after buying an additional 50,952 shares during the last quarter. 7.32% of the stock is currently owned by institutional investors.
ADXS has been the topic of several analyst reports. Zacks Investment Research downgraded Advaxis from a “buy” rating to a “hold” rating in a report on Wednesday. ValuEngine upgraded shares of Advaxis from a “hold” rating to a “buy” rating in a report on Thursday, August 1st.
Shares of NASDAQ:ADXS traded up $0.03 on Thursday, hitting $0.31. 4,468,700 shares of the company were exchanged, compared to its average volume of 1,976,263. The company’s 50 day moving average price is $0.31 and its two-hundred day moving average price is $1.52. Advaxis, Inc. has a one year low of $0.21 and a one year high of $10.80. The firm has a market capitalization of $4.87 million, a price-to-earnings ratio of -0.02 and a beta of 3.16.
Advaxis (NASDAQ:ADXS) last posted its quarterly earnings data on Monday, September 9th. The biotechnology company reported ($1.00) earnings per share (EPS) for the quarter, topping the consensus estimate of ($1.24) by $0.24. Advaxis had a negative net margin of 113.67% and a negative return on equity of 67.08%. The company had revenue of $0.01 million for the quarter. As a group, equities analysts expect that Advaxis, Inc. will post -2.7 EPS for the current year.
https://slatersentinel.com/news/2019/11/01/renaissance-technologies-llc-has-1-05-million-stock-holdings-in-advaxis-inc-nasdaqadxs.html
The ADXS-HOT program is a series of cancer-specific drug candidates that will target common, or shared, somatic mutations, cancer testis antigens and oncofetal antigens. ... DNA sequencing is not required, and the ADXS-HOT products are expected to be “off the shelf” and ready to administer for multiple patients.
Reported on Stocktwits: "Several institutional investors have recently modified their holdings of the company. JPMorgan Chase & Co. boosted its holdings in shares of Advaxis by 53,633.7% during the 2nd quarter. JPMorgan Chase & Co. now owns 51,047 shares of the biotechnology company’s stock worth $107,000 after purchasing an additional 50,952 shares during the last quarter. Vanguard Group Inc. boosted its holdings in shares of Advaxis by 71.1% during the 2nd quarter. Vanguard Group Inc. now owns 230,106 shares of the biotechnology company’s stock worth $481,000 after purchasing an additional 95,607 shares during the last quarter. Finally, Renaissance Technologies LLC boosted its holdings in shares of Advaxis by 143.7% during the 2nd quarter. Renaissance Technologies LLC now owns 501,000 shares of the biotechnology company’s stock worth $1,047,000 after purchasing an additional 295,444 shares during the last quarter. Institutional investors and hedge funds own 7.32% of the company’s stock."
Jumping from a plane without a parachute... It's been done before, successfully:
How about an apology to the LTSHs for unleashing the incomprehensible equity dilution that annihilated our investment in the company?
Advaxis, Inc. Issues Letter to Shareholders
August 22, 2019
PRINCETON, N.J.--(BUSINESS WIRE)--Advaxis, Inc. (Nasdaq: ADXS), a clinical-stage biotechnology company focused on the discovery, development and commercialization of immunotherapy products, today announced that its chief executive officer, Kenneth A. Berlin, issued an open letter to Advaxis’ stockholders. The following letter can also be viewed on the Investor Relations section of the Advaxis website.
Dear Stockholders,
Innovation, particularly in a highly regulated industry such as drug development, often results in ebbs and flows of successes and failures accompanied by investor optimism and skepticism. Groundbreaking approaches such as the use of monoclonal antibodies, targeted therapies and checkpoint inhibition in immune therapy, which now form the foundation of the oncology biotech industry, all experienced similar innovation cycles. In each case, there was a great deal of initial excitement followed by a healthy dose of skepticism before each of these modalities ultimately proved themselves beneficial in the transformation of patient care.
We believe that neoantigen-directed immunotherapy is going through a similar cycle. This is yet another example of an innovative approach to oncology treatment that received significant initial enthusiasm driven by the discovery that neoantigens play a central role in driving the responses in patients who respond to immune checkpoint inhibitors. This initial enthusiasm has waned somewhat over the past year as investors await more tangible clinical results, and as a result the market valuations of companies in the field, including ours and others who recently went public, have significantly underperformed relative to the broader biotech industry. Clearly, there are other factors that may have affected our share price, such as our transition from a company with a late-stage asset to a clinical development company running Phase 1 and Phase 2 clinical trials. We have been navigating this transition with a focus on the innovative field of neoantigen-directed immunotherapies and building on the early promising data we have seen in our ADXS-NEO clinical trial.
Here at Advaxis, we have developed a technology that harnesses the patient’s own immune system in an effort to fight and destroy cancer cells. We believe our technology may be one of the best ways to stimulate the immune system and we are in the process of generating data to demonstrate its clinical potential. Over nearly two decades we have optimized our Lm Technology platform by studying a number of different drug constructs derived from this platform. These efforts and results have taught us that our technology is highly immunogenic (i.e., is able to generate a rapid and robust immune response) and has the capacity to incorporate a large number of antigen targets. We believe these qualities, among others, make our platform well-suited to target the large and diverse number of neoantigen targets found across different patients. Thus far in 2019, we have presented preliminary data on our personalized neoantigen program (ADXS-NEO) in which we observed the ability to generate important T cells that target and kill cancer cells in the first several patients enrolled in the study. We believe this is a critical step in the process of eradicating cancer cells.
Like all technologies, the process to demonstrate clinical proof-of-concept takes time. The results to date reinforce our belief that our platform is able to harness a strong immunological response and are now evaluating the translation of this response into clinical improvement for people with cancer. Although our stock price remains under pressure, we are managing those elements of our business that we can control – which include generating data and advancing our pipeline. As such, we will continue to report data from our programs throughout the remainder of 2019 and into 2020.
We remain steadfast in our commitment to our core priority – demonstrating that our unique platform can impact the fight against cancer. To achieve this, we are prudently managing our expenses to the level which, in our judgment, is appropriate for our programs. Relatedly, we continue to explore different avenues through which to finance our programs and are aggressively pursuing business development efforts that we anticipate will expand our network of partners to assist in moving these programs forward.
Based on the immunological responses observed to date, the data we anticipate generating from our clinical trials over the next several quarters, and the dedication and passion of the entire team at Advaxis, we believe our current strategy will position the company to advance neoantigen-directed immunotherapies into late stage clinical development and ultimately to commercialization.
We look forward to sharing our achievements with you as we continue to execute on our strategy and our mission to improve the lives of people with cancer.
Sincerely,
Kenneth A. Berlin
President and CEO, Advaxis, Inc.
Forward-Looking Statements
It appears they are doing fine delivering the "targeted genetically engineer cannabis flavonoids" without the need for another method. Hope all goes well for those in the study fighting the dreaded pancreatic cancer.
Interesting the video at the bottom of the page/link you provided is a broadcast News report of a new targeted approach for CHEMO to treat pancreatic cancer. Pittsburgh Medical Center uses a catheter to "bath the tumor" providing a locally administered CHEMO that does not circulate through out the body. Results look promising.
Science marches on...
For fun check out NBRV. FDA Approval, trading suspended. Shorts about to get fried!
I think it is pretty clear that the financiers of the latest offering did not loose money or lack understanding.
From their negotiations they knew what management was offering and the discount they would get. Short it from the mid-$1 range and you are guaranteed a nice payout by the time they closed the offering at 70 cents. Controlling interest in the company and a payday all on the backs of LTSHs.
New this morning: Item 3.03. Material Modification to Rights of Security Holders.
On July 25, 2019, the exercise price of warrants issued by the Company in September 2018 (the “Warrants”) was reduced from $0.248 per Warrant (or $3.72 per full share of the Company’s common stock, $0.001 par value per share (the “Common Stock”)) to $0.0248 per Warrant (or $0.372 per full share of Common Stock). The reduction was the result of issuance of the Company’s common stock in its previously announced public offering. The full text of the notice of reduction in the exercise price of the Warrants is attached hereto as Exhibit 99.1 and is incorporated herein by reference.
So how would anyone that is putting up money to extend the runway for ADXS - make money?
Well here is one: ADXS has obviously been looking for $$$ for quite some time. As they shake the trees and get few takers they come across some (additional) toxic financing. Back when the SP was north of $1.50 they start to discuss the basement pricing of .70 cents. The financier easily shorts from these higher levels knowing they will close out the position when news surfaces of the bargain basement pricing. They have already made their money by the time they close the offering. Warrants are a nice kicker to sweeten the deal.
The offering is out:
9,615,384 Shares of Common Stock
Pre-Funded Warrants to Purchase Up to 9,615,384 Shares of Common Stock
Warrants to Purchase up to 4,807,692 Shares of Common Stock.
This is an offering of up to 9,615,384 shares of our common stock, $0.001 par value per share and warrants to purchase up to 4,807,692 shares of our common stock (and the common stock issuable from time to time upon exercise of the warrants). Each share of our common stock is being sold together with a warrant, or a purchase warrant, to purchase up to 0.5 shares of our common stock. Each purchase warrant will have an exercise price per share of not less than 100% of the offering price, will be exercisable immediately, and will expire on the fifth anniversary of the original issuance date. The shares of our common stock and purchase warrants are immediately separable and will be issued separately, but will be purchased together in this offering.
NP! Glad it worked out for you.
The CC announced they have retained a company for "Business Development efforts"...
https://www.treehillpartners.com/
"A healthcare focused advisory firm to assist us with our partnering efforts across our numerous drug constructs".
Last great hope?
Link to a replay of the call: https://edge.media-server.com/m6/p/6juis356
Here's one for ya, Raja. R/S coming on 6/10-11:
Hemispherx Biopharma, Inc. (NYSE American: HEB), an immuno-pharma company focused on the research and development of therapeutics to treat multiple types of cancers and immune-deficiency diseases, today announced that its stockholders voted in favor to grant the Board of Directors the authority to effect a reverse stock split of the company’s issued and outstanding shares of Common Stock. The proposal passed by approximately 55% of all issued and outstanding shares and approximately 86% of the shares actually voted were voted in favor of the reverse split.
Advaxis Announces Two Poster Presentations at the Frontiers in Cancer Immunotherapy Conference
May 14, 2019
• Updated data from Phase 1/2 ADXS-PSA study combination arm show prolonged survival in heavily pretreated prostate cancer patients with microsatellite-stable (MSS) disease
• Updated early findings from Phase 1 ADXS-NEO study show encouraging safety, immunogenicity and clinical signals in MSS colorectal cancer patients
"Safety and Immunogenicity of a Personalized Neoantigen-Listeria Vaccine in Cancer Patients"
PRINCETON, N.J.--(BUSINESS WIRE)--Advaxis, Inc. (NASDAQ: ADXS), a late-stage biotechnology company focused on the discovery, development and commercialization of immunotherapy products, announces the presentation of two posters at the Frontiers in Cancer Immunotherapy conference, being held today at the New York Academy of Sciences in New York City. Both posters were first presented at the recent American Association for Cancer Research (AACR) Annual Meeting, and each has updated findings being presented today.
The first presentation regarding a poster entitled “Effects of ADXS-PSA With or Without Pembrolizumab on Survival and Antigen Spreading in Metastatic, Castration-Resistant Prostate Cancer Patients (Results from KEYNOTE-046)” is conference poster #31, and will be presented by Robert Petit, Ph.D., Advaxis Chief Scientific Officer, and Mark N. Stein, M.D., FACS, Associate Professor of Medical Oncology at Columbia University Medical Center, from 4:45 to 5:30 p.m. Eastern time.
The Phase 1/2 KEYNOTE-046 study is being conducted in conjunction with Merck (known as MSD outside the U.S. and Canada) in metastatic, castration-resistant prostate cancer (mCRPC). This trial and is evaluating ADXS-PSA, one of Advaxis’ Listeria monocytogenes (Lm)-based immunotherapies, alone and in combination with KEYTRUDA® (pembrolizumab), Merck’s anti-PD-1 therapy.
KEYNOTE-046 is an open-label, multicenter, dose-determining safety and tolerability Phase 1/2 trial of 50 heavily pretreated patients conducted in two parts (Part A and Part B), with a Phase 2 expansion cohort. The objective of the study is to evaluate ADXS-PSA alone (Part A) and in combination with KEYTRUDA® (Part B) for primary endpoints that include safety, tolerability and dosing. Secondary endpoints include anti-tumor activity and progression-free survival, and exploratory endpoints include associations between biomarkers of immunologic response (serum PSA) with clinical outcomes.
Key findings from 37 patients treated in the combination arm (Part B) of KEYNOTE-046 as reported at AACR include the following:
• The majority of treatment-related adverse events consisted of transient and reversible Grade 1-2 chills/rigors, fever, hypotension, nausea and fatigue. The combination of ADXS-PSA and pembrolizumab has been well-tolerated to date, with no additive toxicity observed.
• Median overall survival (OS) was 21.1 months at data cutoff (February 1, 2019) (95% CI, range 16.0 months to not-yet-reached) in this dataset of 37 patients.
• Correlative immune analyses showed T-cell responses against PSA in 75% of subjects and antigen spreading in 85% of subjects.
• Broader immune stimulation, including B-cell activation, was observed in the combination arm (n=37) than in the ADXS-PSA monotherapy arm (n=13).
Updated findings being presented at the Frontiers in Cancer Immunotherapy conference include:
• Microsatellite Instability-High (MSI-High), the condition of genetic hypermutability that results from defective DNA mismatch repair, is observed in 5-12% of all mCRPC patients and often leads to a higher likelihood of response to immunotherapy. In this study, 36 of the patients in the combination arm, which observed prolonged survival, were MSI-High negative (with one subject not tested), thereby making them unlikely to respond to checkpoint blockade.
• There are 16 patients in the combination therapy part of this trial who are alive and continue to be monitored.
“The latest results from our KEYNOTE-046 study demonstrate that practically all the patients in the combination arm of this study are microsatellite stable and therefore are not expected to respond to treatment with a checkpoint inhibitor,” said Kenneth A. Berlin, President and Chief Executive Officer of Advaxis. “These data suggest that the combination of ADXS-PSA and pembrolizumab appears to show activity and to be associated with prolonged OS in this population.”
The second poster discussion entitled “Safety and Immunogenicity of a Personalized Neoantigen-Listeria Vaccine in Cancer Patients” is conference poster #9, and will be presented by Frank Tsai, M.D., Medical Oncologist and Investigator at Honor Health Research Institute and one of the lead investigators of the ADXS-NEO clinical study, from 4:45 to 5:30 p.m. Eastern time.
ADXS-NEO is a live, attenuated Lm immunotherapy using personalized antigen delivery based on whole-exome sequencing of a patient’s tumor to identify personal neoantigens. The ongoing Phase 1 trial is designed to evaluate the safety, tolerability and preliminary clinical immunological activity of ADXS-NEO alone (Part A) and in combination with anti-PD-1 antibody therapy (Part B) in subjects with certain types of advanced or metastatic solid tumors. Part C of the trial will be an expansion of the combination therapy arm and will be initiated based on emerging data from the first two parts of the trial.
Preliminary findings from the ADXS-NEO Phase 1 study as reported at AACR include the following:
• Substantial anti-tumor immunity, including T cell responses to neoantigens and antigen spreading, was observed within one week of first dose at both dose levels.
• Dosing of ADXS-NEO at 1x108 colony forming units (CFU) has been well-tolerated in two patients.
• ADXS-NEO dosed at 1x109 CFU was beyond the maximum tolerated dose (MTD) ? Reversible Grade 3 hypoxia (n=2) and Grade 3 hypotension (n=1) were dose-limiting toxicities (DLTs).
• Manufacturing of ADXS-NEO, comprised of 40 personal neoantigens, was successfully completed within seven to eight weeks for each subject.
Updated findings being presented at the Frontiers in Cancer Immunotherapy conference include:
• Data from the two MSS colorectal cancer patients dosed with ADXS-NEO at 1x108 CFU demonstrated increased CD8+ T cell infiltration in the tumor microenvironment after three doses of ADXS-NEO. Both patients had metastatic colorectal cancer, which is considered to be a “cold” tumor and typically exhibits little CD8+ T cell infiltration and resistance to immunotherapy, yet both successfully transitioned from “cold” tumors into “hot” tumors with ADXS-NEO therapy. An estimated 80-85% of colorectal cancer patients are MSS.
• Two patients (one treated at 1x109 and one at 1x108 CFU) achieved stable disease per RECIST 1.1 criteria. Another patient has yet to be evaluated but has experienced normal performance status and an active lifestyle over the three months of therapy with ADXS-NEO at 1x108 CFU.
“Although we have just started to define the safety, immunogenicity and changes in the tumor microenvironment with ADXS-NEO monotherapy, it is possible that these effects may have a positive impact in the sensitivity to checkpoint inhibitors in ‘cold’ tumors,” said Dr. Tsai. “We look forward to further documenting the effects of ADXS-NEO monotherapy in MSS metastatic colorectal cancer (CRC) and in other tumors. Also, since the majority of patients with MSS-CRC do not respond well to immunotherapy, we are also looking forward to starting the combination therapy of ADXS-NEO and a checkpoint inhibitor, as called for in the current study.”
Mr. Berlin added, “We are pleased to report encouraging updated findings from both of these ongoing studies at the Frontiers in Cancer Immunotherapy conference. We are encouraged given that we are seeing clinical benefit from our immunotherapy drug candidates in difficult-to-treat patient populations in furtherance of our mission to helping improve the lives of people with cancer. We look forward to sharing further data from our programs throughout the balance of the year.”
Both posters will be available at www.advaxis.com today at 4:45 p.m. ET.
About KEYNOTE-046
KEYNOTE-046 (NCT02325557) is a Phase 1/2 open-label, multicenter, dose-determination and expansion trial that evaluates the safety, tolerability and preliminary clinical activity of ADXS-PSA as monotherapy (Part A; n=14 [13 treated]), and in combination with KEYTRUDA® (Part B; n=37) in heavily pretreated patients with progressive and refractory mCRPC.
About ADXS-PSA
ADXS-PSA, one of Advaxis' Lm-based immunotherapies, utilizes live, attenuated, bioengineered Lm as a vector to deliver PSA directly to antigen presenting cells. Development is being pursued in a clinical trial collaboration and supply agreement with Merck.
About ADXS-NEO
ADXS-NEO is an investigational personalized Lm-based immunotherapy designed to generate immune response against mutation-derived tumor-specific neoantigens identified through DNA sequencing of a patient’s own tumor. The program focuses on creating a customized treatment for each patient targeting multiple neoantigens found in a biopsy of the patient’s tumor.
About Advaxis, Inc.
Advaxis, Inc. is a late-stage biotechnology company focused on the discovery, development and commercialization of proprietary Lm-based antigen delivery products. These immunotherapies are based on a platform technology that utilizes live attenuated Listeria monocytogenes (Lm) bioengineered to secrete antigen/adjuvant fusion proteins. These Lm-based strains are believed to be a significant advancement in immunotherapy as they integrate multiple functions into a single immunotherapy and are designed to access and direct antigen presenting cells to stimulate anti-tumor T cell immunity, activate the immune system with the equivalent of multiple adjuvants, and simultaneously reduce tumor protection in the tumor microenvironment to enable T cells to eliminate tumors. Advaxis has four programs in various stages of clinical development: ADXS-HPV for cervical cancer; ADXS-NEO, a personalized neoantigen-directed therapy for multiple cancers; ADXS-503 for non-small cell lung cancer, from its ADXS-HOT off-the-shelf neoantigen-directed program; and ADXS-PSA for prostate cancer.
Yeah, but what does that mean for LTSH? Is it a net nothing and once the reverse-merger happens its about waiting to see if the science pans out, again? I dont know much about reverse-mergers but I dont think they pay a premium or you come out on top in the merged company, financial wise.
It dilutes the LTSH to a minority stake but presumably, they are now part of a company with promising technology & the existing technology is either scrapped (or pared down) and now has access to (some) new cash:
A reverse merger is the most common alternative to an initial public offering (IPO) or direct public offering (DPO) for a company seeking to go public. A “reverse merger” allows a privately held company to go public by acquiring a controlling interest in, and merging with, a public operating or public shell company. The SEC defines a “shell company” as a publically traded company with (1) no or nominal operations and (2) either no or nominal assets or assets consisting solely of any amount of cash and cash equivalents.
In a reverse merger process, the private operating company shareholders exchange their shares of the private company for either new or existing shares of the public company so that at the end of the transaction, the shareholders of the private operating company own a majority of the public company and the private operating company has become a wholly owned subsidiary of the public company. The public company assumes the operations of the private operating company. At the closing, the private operating company has gone public by acquiring a controlling interest in a public company and having the public company assume operations of the operating entity.
I called this last week. Only hope at this point is a reverse-merger with a private biotech company looking for an easy way to go public, as Dew predicted.
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=148706494
I would think any managers who have any respect for there personal skills and careers would be working on an exit strategy about right now. Who wants to be the last man standing when the lights go out?
Personally, I have been on projects that turned sour for the incumbents and I took this as my Que to move on to greener pastures.
Usually, the ones left behind to the bitter end were of 'questionable' skill set.
Much better to leave on your own terms, especially if any of the calamity can be associated with the work you did or the decisions you made while at the helm.
It would not surprise me if Petit or Gutierrez flew the coop sooner rather than later.
Of course they are both presenting at Industry Conferences in the next couple weeks. Needs to be something earth shattering to turn the tide at this point.
I would think any managers who have any respect for there personal skills and careers would be working on an exit strategy about right now. Who wants to be the last man standing when the lights go out?
Personally, I have been on projects that turned sour for the incumbents and I took this as my Que to move on to greener pastures.
Usually, the ones left behind to the bitter end were of 'questionable' skill set.
Much better to leave on your own terms, especially if any of the calamity can be associated with the work you did or the decisions you made while at the helm.
It would not surprise me if Petit or Gutierrez flew the coop sooner rather than later.
Of course they are both presenting at Industry Conferences in the next couple weeks. Needs to be something earth shattering to turn the tide at this point.
Interesting Article on CAR T cell therapy 2.0 (link at bottom):
The story of one physician-turned-researcher’s journey down the CAR T innovation continuum
Dr. Lei Yu, MD, PhD
Director of the Institute of the Biomedical Engineering and Technology (iBET), Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, China;Shanghai Unicar-Therapy Bio-Medicine Technology Co., Ltd.
Since last year’s personalized immunotherapy success story surrounding Emily Whitehead, CAR T cell therapy has embarked on a new era. There’s an exciting surge of scientific effort toward understanding chimeric antigen receptor (CAR) technology and its potential to advance cures. Enter Dr. Yu, equal parts medically trained surgeon and astute researcher. His cross-cultural efforts between China, the US, and Canada are driven by a passion for translational medicine rooted in gene therapy research. While recounting his endeavor to bridge the gap between the bench and the clinic, Dr. Yu reflects on the promise of an innovative CAR T cell therapy 2.0 and why he continues to pursue a more precise immunotherapy.
You have an impressive résumé—it starts in medicine and branches out into basic research. What inspired you?
After conducting cardiac surgery on many patients, I noticed that almost every patient has to go back to the ICU. Infection and sepsis are hard to control within patients undergoing this type of surgery. It led me to the study of how to control and prevent these infections in the hospital.
Can you take us through your scientific journey?
Helping patients was my motivation so I applied for a PhD in medical microbiology and immunology at the University of Alberta [Canada]. My focus was vaccine research. After graduation, I thought, what next? At that time, gene therapy was quite hot. I applied to UCSD, Theodore Friedmann’s lab. Professor Friedmann is a pioneer of gene therapy and he coined the “gene therapy” term in 1972. We used genetic engineering to increase safety in the design of viral vectors. Afterward, I studied gene delivery with Professor Sam Wang Kim. As I continued to develop gene therapy technology, I partnered with a Japanese company to set up a location in Oceanside, California. We started with five employees and have grown to 115.
It sounds like you are really driven to help patients. Also, your work carries across multiple countries; can you please tell us how your work in China and the US impacts translational research?
In China, they have many patients and also they have a faster clinical trial process. In the US, sometimes we’re waiting for patients and the process can be long and slow. [So] I’m back in China to set up training for more of the scientists within translational medicine. I try to make the technologies get to clinic faster. This is the reason why I’m in basic research and translational medicine and pharmaceutical development.
Your approach is from a number of perspectives. Why is that?
I feel this is helping me to be multidisciplinary. Currently, many of the life science technologies need more and varied scientific knowledge to design and to reduce the risk of failure. Also, the industry as a whole challenges me to think more systematically, like a systems engineer. You cannot just take care of one part and forget another. You need to consider the big picture to move ahead. I feel this gives me a greater chance of success for helping people.
What’s your proudest moment so far?
Working at a hospital, you see very sad scenes. That motivates me to research gene therapy technology—gene therapy from the vector part, the gene part, the genetics part, and also the clinical part. Gene therapy has been around for 30 years. CAR T cell therapy is a form of gene therapy. This is why I say it’s the right timing for us. I’ve worked with a patient who was close to death; but after the infusion of the CAR T cells, the patient was very much alive and was even able to stand. This is why I try to do my best, and have branched out from lymphoma and myeloma to leukemia and solid tumors. So many patients are waiting, and there are many lives to save. I’m so happy with what I do because almost 87% of my patients have been saved.
You’ve mentioned CAR T cell therapy. What’s CAR T 2.0?
I think of the first CAR T cell therapy as version 1.0 because usually they just modify CAR T molecules. This has already proven to be successful. However, even though we can continue to improve their therapeutic effect, we cannot prove their safety. How do you balance it? This is why we think about how to go about making the T cell more fit for reduced risk by increasing safety. You cannot just modify the CAR T molecules because if you modified the CAR T molecules you may reduce risk but also you’ll reduce efficacy.
For solid tumors, they have a microenvironment that is not good for the activity of CAR T cells. We consider how to make CAR T cells that can ignore inhibitory effects present in the tumor microenvironment (TME). For example, PD-1 is mainly expressed by the T cell. PD-L1 is mainly expressed by the cancer cell and also the TME. Even though you have a lot of the PD-L1 in the tumor tissues, if we can reduce the PD-1 expressed on T cells, then they can go into the tumor uninhibited and keep functioning. This is why we are also using silencer RNA to study this as we continue to genetically engineer T cells that are better fit for their environment. This is what we call 2.0.
What are the biggest challenges you face as you work toward CAR T 2.0?
Lots of issues here. Many of the current manufacturers producing modified CAR T cells are simply from basic research backgrounds. For industry, I think we require more of a single-use technology so we can avoid contamination. Second, simplification of the process is important. Third, cells from each patient are different so it’s challenging to make controls. In this case, you have to have a very experienced scientist observe cells to make a judgment call. Or, using AI is promising because that sort of system will remove variability. In Chinese medicine, for example, an experienced doctor who is very old and with lots of experience would like to pass down knowledge to their student. However, it’s difficult to pass down personal intuition and feeling. But if you can tell a machine to “understand” by accumulating data, you can design this machine and make the passing on of knowledge easier by modern methods.
What is your perspective on the future of CAR T and its impact?
I think safety is still a problem. It’s hard to reduce the risk and make CAR T therapy more benign so you can treat the patients, but also not harm them. This is still a clinical bottleneck or pain point. Another challenge is finding the right targeting molecule. It’s important to distinguish exactly what the CAR T is fighting. Biomarker discovery is challenging because you have to look at the specific cancer, numerous biomarkers, and the TME. For example, you have to look at overexpression. It means a cancer cell can make 100 times more biomarkers than a normal cell because the normal cell is still healthy. Also, neoantigens: these antigens change so frequently. Once you hit the right target, you may hit 100 cancer cells but another 100 will change. This is why it’s quite difficult. I really think this is where T cell receptor (TCR) therapy in combination with CAR T therapy could help. This is maybe where the future lies.
Is there anything outside of the science that really drives you and motivates you?
I like reading, swimming, and walking. This is also my time to think. I’ve read and written lots of kung fu stories about teaching someone how to fight a bad guy and helping weaker people. This is the same as a doctor or scientist: the goal is to treat the patients, to save the patients. This can be summed up in two purposes: one purpose is to try to make the people live longer; the second is to try to make their quality of life better. In other words, to make patients happy. Healthy, happy. This is why I use my knowledge and greatest effort to reach this goal one step at a time.
https://www.thermofisher.com/us/en/home/new-ideas/life-in-the-lab/january-2019-stay-curious/car-t-2-technology.html?cid=BID_CDI_SBU_R01_CP1231_PJT4301_COL18031_0SO_FBK_DA_NUR_AB_S18_10031017
Well, that is putting your money where your mouth is. Best wishes for a 'green' day/week.
From Whale Wisdom:
Shares value rank Source Date
600,000 2,430,000.00 6 13G 2019-04-03
https://whalewisdom.com/filer/empery-asset-management-lp
Now wait a minute... I thought we already proved that Short Attacks, short-selling schemes, manipulation, & articles & posts of false and misleading statements are akin to unicorns & pixie dust? Surely these lawsuits have no merit...
It appears to be a fake listing that someone copied from an existing iCMS job listing.
How about the 'M' word? Manipulation anyone?
Hey look at it this way... Some folks wished for the day ADXS stock price would be above ADRO's. Today, they got their wish.
That's an older article. This newer articles point to the SEC crack downs...
With the Securities and Exchange Commission cracking down on penny stocks, Merrill Lynch recently told its clients and financial advisers that it is putting restrictions on the purchase and sale of a large swath of low-priced securities.
"To ensure we are complying with SEC regulations and protecting the interests of our clients, we recently made changes to our policy regarding low-priced securities," a Merrill Lynch spokesman, Jerry Dubrowski, wrote in an email. As a result, certain transactions may be subject to restrictions, trading prohibitions or other limitations."
According to a source familiar with the moves, as of July, clients were no longer able to buy penny stocks through Merrill Lynch, and by the end of September, will no longer be able to sell them through the brokerage. The stocks will still be able to be transferred to a different account at another broker-dealer.
From this past Sept:
https://www.investmentnews.com/article/20180928/FREE/180929915/merrill-lynch-no-longer-will-accept-penny-stock-trades
https://www.cnbc.com/2018/09/28/bank-of-america-cracks-down-on-penny-stocks-with-purchase-ban.html
The first chance some Heggies/Inst. can get back in now that ADXS is no longer a penny stock.
Some Trading Platforms will not let you short sell 'Against the Box'. Meaning you cannot sell short a stock that you currently own.
Wait to see the volume on the downside. Typically it's 1/2 the volume of the upside which does not point to a fair market. Upside volume was impressive.
Thanks for explanation, Investorluck!
Since we are talking Theories, here's one:
A giant like Amgen wants (and needs) to keep an eye on any and all the latest discoveries in Immunotherapy to ensure that when some late breaking promising therapy comes along they own it (or a piece of it). In the Spring of 2016, ADXS-NEO was that technology. There were a handful of companies using this tech to deliver tumor antigen/adjuvant fusion proteins within antigen presenting cells. ADXS just had a lab results to say this is promising tech. Amgen jumps in early and secures Worldwide rights. Their offer is an upfront payment to Advaxis of $40 million and purchase agreement to buy $25 million of Advaxis common stock. They are smart enough to back-load all milestone payments and throw out a large number (up to $475 million), in the negotiations hoping their counterpart will be enthralled with all those zeros and not press the issue of timing on those milestone payments and the clause that they can bow out when ever they want. They also ensure ADXS pays for everything through proof-of-concept.
From that point forward, they are looking for any reason that this tech is not all that... cost too much, takes too long, market size, can't be confirmed, etc. It needs to be a bonafided blockbuster that will ring up quick sales or they just execute their exit. And if they sold the stock at the right time - it only cost them $40 mil in total.
Not a bad plan to stay on the cutting edge of Immunotherapy at a manageable cost. Rinse & repeat the next time around.
It is no longer available - but I had it opened in a browser so here you go:
Bristol-Myers drives into CAR-T therapies
February 18th 2019 | United States | Pharmaceuticals and biotechnology | Bristol-Myers Squibb
Will the megamerger between Bristol-Myers Squibb and Cellgene bring results, particularly in CAR-T therapies?
Bristol-Myers Squibb sent a shockwave through the pharma industry at the start of 2019 with its US$74bn acquisition of Celgene. One of the largest-ever pharmaceutical acquisitions, the deal dwarfed Takeda's takeover of the UK's Shire for nearly £46bn (US$62bn) – which was completed the same month. Bristol-Myers claims that the deal will expand its pipeline of drugs that target cancer and cardiovascular, immunologic and inflammatory disorders. The acquisition will add to its portfolio six drug candidates that are nearing their launch, including a CAR-T treatment for multiple myeloma.
CAR-T and how it works
Chimeric antigen receptor (CAR) T cell therapy is a targeted treatment that uses the patient's immune system to kill cancer cells. To do this, doctors harvest and genetically modify patients' T-cells, which are part of the body's immune system, in order to create structures called chimeric antigen receptors (CARs) on their surface. When these CAR-T cells are infused back into the patient, the receptors recognise and attack specific proteins on the cancer cells.
In 2017 the American Society of Clinical Oncology (ASCO) recognised CAR-T as the "Advance of the Year" for its demonstrated potential in treating blood cancer and several types of solid tumours. The US Food and Drug Administration approved the first two CAR-T drugs in the same year: Novartis' Kymriah and Yescarta from Gilead and Kite Pharma. However, the potential of the technology is only just starting to be fully exploited. As well as existing indications, it is now being evaluated for the treatment of more common solid tumours, such as breast cancer.
Bristol-Myers's CAR-T inheritance
Cellgene in particular has been exploring CAR-T therapy by running clinical trials of a drug candidate for multiple myeloma, currently known as bb2121. It has been working with Bluebird Bio, a US drug developer, to develop the drug. As of November, Celgene had just completed enrolment for a mid-stage clinical trial to evaluate its safety and efficacy of bb2121. However, the drug has already been granted breakthrough therapy designation in the US, giving it a fast track to be approved in 2020 if the clinical trials are successful.
Cellgene has also partnered with Juno Therapeutics to develop CAR-T drugs that target a certain type of cancer protein called CD19. In early 2018 it announced that it would acquire the company for about US$9bn, doubling down on the novel therapy. At the time the acquisition price was double Juno's market capitalisation.
Meanwhile, Cellgene is also strengthening its CAR-T manufacturing capabilities. It established a new immunotherapy manufacturing facility in Summit, New Jersey, built on an abandoned biopharmaceutical campus. (Its compatriot, Merck & Co, had abandoned the complex in 2013 to move to Kenilworth as part of a restructuring and workforce reduction.) With this facility, Cellgene hopes to scale up its CAR-T clinical trials and its eventual drug production.
Costs of CAR-T
CAR-T is not cheap, however, which has proven a barrier to uptake. Yescarta (axicabtagene ciloleucel), which was launched in the US in 2017 for B-cell lymphoma, is priced at US$373,000 per treatment, while Kymriah, which is approved for relapsed or refractory B-cell lymphoblastic leukaemia, is priced at US$475,000 per treatment. For providers, these drugs come with additional costs as well, such as the cost of responding to any of the adverse events that can occur with cancer treatment. Cytokine release syndrome, a common condition caused by immunotherapy, is linked to fever, nausea, low blood pressure and other effects.
The long-term effectiveness of these drugs is still not certain either, although findings from a large clinical trial by Kite Pharmaceuticals have confirmed the positive results of Yescarta in treating some patients with lymphoma. In June, Novartis, too, revealed positive 14-month results from a clinical trial of its drug, saying that patients had a 65% change of being disease-free for a year after the initial response.
The promise of CAR-T could explain why Novartis' Kymriah has been approved for coverage by the UK's National Health Service (NHS), despite draft guidance from the independent National Institute for Health and Care Excellence (NICE) saying that CAR-T, particularly Gilead's Yescarta, is too costly to justify coverage. The details of the NHS deal are not yet clear, but it will involve a pay-out from Novartis if the therapy does not work.
Scott Gottlieb, the current commissioner of the US Food and Drug Administration (FDA), also weighed in on the issue in an interview in 2018. Mr Gottlieb reportedly expressed concerns over the price of CAR-T therapies and warned that failure to develop payment structures could slow down the treatment's development. He said that the FDA may be able to help development payment plans, although he did not specify details. He also noted that the federal agency would be open to outcomes-based payments, wherein pay-outs are tied to a patient's health outcome over a certain period of time. Even so, the FDA rejected an outcomes-based proposal from Novartis earlier in 2018.
The manufacturing bottle-neck
Apart from payer challenges, Novartis and Gilead, and now Bristol Myers, will also have to invest in manufacturing infrastructure. Producing the therapy requires collecting cells from the patient, shipping them to a facility, combining it to make the CAR-T product and then shipping back the final product to the health facility. It is not cheap or easy.
Indeed, the costs have put off other potential CAR-T developers, such as Eli Lilly and Co. Its chief executive, Dave Ricks, voiced concerns over scaling up manufacturing of CAR-T drugs to meet demand, even as it agreed to pay US$8bn to acquire Loxo Oncology in January. As for Novartis, it has already been hampered by a lack of manufacturing capacity to meet demand for its CAR-T therapy. It ended 2018 with an announcement that it would acquire a contract manufacturer in France to step up production of Kymriah.
To make production easier, drugmakers may eventually be able to rely on donor cells rather than individual patients' T-cells, but work on this modification is still in its early stages. For now, drugmakers in the field or those planning to enter the market will have to invest heavily. With its acquisition of Cellgene's manufacturing capabilities, Bristol-Myers may have solved that part of the puzzle for now, but scaling up will be a challenge for every entrant in the market.
Sizing up the competition
Yet despite these challenges, competition in the CAR-T field is increasing. As well as Bristol-Myers, Kite, Gilead and Novartis, other new entrants include AbbVie. In mid-2018 it announced collaboration with the California Institute for Biomedical Research (Calibr) for next-generation CAR-T therapies, this time focused directly on solid tumours. The immuno-oncology push will be even more important for AbbVie after the failure of Rova-T, a major cancer drug candidate, in late-stage clinical trials.
Pfizer too is exploring CAR-T therapy with an asset contribution deal with Allogene Therapeutics Inc. It is targeting allogeneic therapies that eliminate the need to personalise treatments for patients, using donor cells to simplify the manufacturing process altogether. If successful, the US drugmaker may be able to solve a major bottleneck in the development of the CAR-T therapy market and gain a significant market share despite being a late entrant. Allogene's portfolio consists of 16 CAR-T therapy assets and an allogeneic candidate undergoing early-stage clinical trials to treat acute lymphoblastic leukaemia.
Despite these potential rivals, it is Bristol-Myers that is now forging ahead into the CAR-T field. With the help of Cellgene, it already claims to be among the top five companies in terms of immunology and inflammation. And if CAR-T ever lives up to its promise, the US company is primed.
How does this company that is for sale and down to 10mil in cash still have a MC 4X ADXS?
CheckPoint Inhibitor
Of interest at the end of each day's agenda on the Immuno-Oncology 360° website:
"Attendees will have the opportunity to network and schedule one-on-one partnering meetings during the networking lunch and scheduled breaks".
Time to make some friends...
https://theconferenceforum.org/conferences/immuno-oncology-360/2019-agenda/#day-72471-tab