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Rich Steffens

 
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  • Galena: Setting The Record Straight [View article]
    I've written about NeuVax before, although with no actual position in the stock. As far as a play, keep an eye on the AACR Annual Meeting. Dr. Mittendorf has a presentation related to NeuVax. The abstract isn't available, but the title is on the itinerary planner.
    Mar 19, 2014. 08:13 PM | 1 Like Like |Link to Comment
  • Galena Biopharma: The Oncologist's Perspective On A Life Saving Therapy [View article]
    The "off-the-shelf" cancer immunotherapy peptide vaccines, such as NeuVax, AE37, and GP2, are easier to administer and less costly to produce than comparable investigational dendritic cell-based approaches or monoclonal antibodies (ie. Herceptin). Dendritic based vaccines require a heavy blood draw which is sent to a lab adding cost and inconvenience, and none of that is necessary in an off the shelf peptide vaccine. The high cost of Herceptin is known in bc HER2 over-expressors in the adjuvant setting, or with Provenge for metastatic prostate cancer (also expresses HER2), so if approved the peptide vaccines have steep cost advantages, as well as far lower levels of toxicity (mainly Grade 1 and 2).

    Although, as Dr. Mittendorf has stated, she also envisions a future where E75 or AE37 are combined with inhibitors of PD-L1, PD-1, CTLA-4, etc, as the checkpoint blockades take the brakes off the immune system as the peptide vaccine steps on the gas pedal (activates T Cells to kill only cancer). Dr. Mittendorf gives a mention of this in a new MD Anderson video from this week (minute 1:22):

    http://bit.ly/MdUCGn

    She was the author of new PD-L1 research, (http://bit.ly/MdUCGp) and that's the context in her bringing up this interest in combining the findings with MD Anderson's Her2/neu peptide vaccine research.

    Low cost, low toxicity, measurable efficacy trends that must be proven in final studies, and a myriad of combinational opportunities, are how I define the vaccines.
    Feb 20, 2014. 01:06 AM | 4 Likes Like |Link to Comment
  • Galena Biopharma: The Oncologist's Perspective On A Life Saving Therapy [View article]
    "Obviously we cannot compare these two studies, but Dr. Hanna's study can be seen as a preview of how clinical trials can progress through the oncology community. A subset analysis showing a statistically significant benefit can translate into a very successful Phase III trial." -Dr. Farhat

    Very interesting, since much is made of the subset analysis. Here's another example:

    Herceptin Early Trials

    "In parallel to two small phase II that established the activity of trastuzumab in humans (Baselga et al 1996; Pegram et al 1998), a large, randomized, single-agent study was initiated in April 1995. Response rate was found to be 15%, and median overall survival was 13 months. In the Her2 3+ subgroup, a considerably higher activity was observed, with an overall response rate of 18% and median survival of 16.4 months. Those results suggested that this group might derive the greatest benefit from trastuzumab (Cobleigh et al 1999)."

    http://1.usa.gov/1jREHN0
    Feb 19, 2014. 07:56 PM | 10 Likes Like |Link to Comment
  • A Deeper Look At The Galena Biopharma Controversy [View article]
    Hi RP,

    Hope all is well. I bought a little GALE for a quick trade that I put in SA Stock Talk. I took the money out after a quick gain since there is too much volatile action around white noise. I'm not a trader, so that was unusual. I'm more interested in the real data for the immunotherapeutic vaccines.

    The AACR Annual Meeting has an interesting topic in the Major Symposia:

    Immunoprevention in Cancer
    Chairperson: Elizabeth M. Jaffee, Johns Hopkins University, Baltimore, MD
    Elizabeth M. Jaffee, Johns Hopkins University, Baltimore, MD
    Ian Frazer, University of Queensland, Brisbane, Australia
    Robert Schoen, University of Pittsburgh, Pittsburgh, PA
    Elizabeth A. Mittendorf, UT MD Anderson Cancer Center, Houston, TX
    http://bit.ly/1bWEFez

    Perhaps Dr. Mittendorf discusses AE37 and/or E75.
    Feb 16, 2014. 09:41 PM | Likes Like |Link to Comment
  • A Deeper Look At The Galena Biopharma Controversy [View article]
    Thank you, Steven. The other obvious error of omission the author makes is that the AE37 Phase II was open at 15 sites, and the NeuVax Phase III is open at 119 sites.
    Feb 15, 2014. 01:19 AM | 3 Likes Like |Link to Comment
  • A Deeper Look At The Galena Biopharma Controversy [View article]
    Most of what is said about AE37 is out of focus. Generex was delisted, hence enrollment slowed as they tried to survive. Their Phase II is the largest vaccine study for breast cancer, and according to MD Anderson's Dr. Elizabeth Mittendorf the AE37 study is very popular with oncologists and patients. I quoted her in m y article about the vaccine last month,

    "One thing I wanted to emphasis is that my colleagues in the breast group at MD Anderson have been very enthusiastic about the AE37 trial, as have been the patients. In fact, we have consistently had a 20 patient wait list in order to get on this study, so it's been a very popular and well received trial."

    The dfs analysis is the main item to watch, and a p value of statistical significance is quite the hurdle at 17 and 24 months out in a couple hundred subjects. AE37 has a lower relapse rate for high HER2 expressors vs. standard of care (Herceptin), about 1% less. That's great, yet the p value shows no difference since Herceptin obviously works. Low expressors get no Herceptin, and the improvement in disease free survival is very encouraging. That type of benefit in a controlled randomized study is usually limited to patients receiving Herceptin, and in this case low HER2 expressors and triple negative only get AE37. For example, 36 month dfs for HER2 overexpressors with Herceptin is 87%. AE37 will match that for all HER2 subjects, if current trends continue. P value comes with thousands of subjects, and AE will report current results at ASCO.

    Sorry, this is a phone, so hopefully typos are understood.
    Feb 14, 2014. 10:17 AM | 21 Likes Like |Link to Comment
  • Galena: Read, Decide, Invest [View article]
    "I believe the FDA issued SPA status and approved the Phase 3, contingent to targeting only those patients with HER2 lymph-node positive, low-expressing tumors (IHC 1-2+), because they determined the data from this subset as statistically significant ... despite its’ small size. Only Herceptin-free patients meeting this criteria are eligible for enrollment in the NueVax Phase 3l (not to be confused with the Combined NueVax/Herceptin Phase 2). Patients with this specific profile have a huge “unmet” need for adjuvant therapy!"
    That's right. Also, keep in mind that HER2 1+ and 2+ are Herceptin-free already, which is why they say the peptide vaccines target an an unmet need. For NeuVax, low HER2 expressors that are node positive that have the HLA-A2 or HLA-A3 haplotype. For AE37, low HER2 expressors that are node positive and high risk node negative with no HLA restrictions. The pending AE37 results will have a much larger population sample size. In the future, oncologists may have more targeted weapons to use in the war against breast cancer.
    Feb 5, 2014. 04:36 PM | 3 Likes Like |Link to Comment
  • Galena: Read, Decide, Invest [View article]
    "In this context, a total of 11 Herceptin-treated patients received the NeuVax vaccine in NCT00841399 and NCT00854789 combined; to the best of my knowledge, these data have not been published."
    The data was published in 2010 for HER2 3+. The data serves as the basis for the combination study of NeuVax and Herceptin being studied in an ongoing Phase II study.
    "It appears that patients with HER2-overexpressing tumors benefit from vaccination in addition to trastuzumab; we did not observe any disease recurrences in 11 patients who received both compared with recurrences in almost 20% of patients with HER2-overexpressing tumors vaccinated in the absence of trastuzumab. Because only 3 patients with HER2-overexpressing tumors received trastuzumab without vaccination, we are limited in the conclusions that can be drawn regarding the benefit of adding vaccination to standard of care trastuzumab therapy. However, data from the combined analysis of the National Surgical Adjuvant Breast and Bowel Project B-31 and North Central Cancer Treatment Group N9831 trials can be used to put our data into context. These trials evaluated the efficacy of trastuzumab in the adjuvant setting. At 3 years, the DFS in patients with HER2-overexpressing tumors who received trastuzumab was 87%.7 The number of patients in our trial is small; therefore, the data must be interpreted with caution. However, taken together with the results of the adjuvant trastuzumab trials, these data suggest that patients with HER2-overexpressing tumors who receive trastuzumab might derive additional benefit from vaccination." Cancer. 2012 May 15; 118(10): 2594–2602
    "During the conduct of this trial, Herceptin® (trastuzumab; Genentech/Roche) became commercially available for HER2 IHC Positive (3+) patients, and the trial was modified accordingly to allow these patients to receive Herceptin, and exclude this patient group from future enrollment and analysis." - Galena http://bit.ly/1fsZX5K
    Feb 4, 2014. 09:28 PM | 1 Like Like |Link to Comment
  • Galena: Read, Decide, Invest [View article]
    This is like the movie Groundhog Day.
    12 of 30 HER2 3+ subjects received Herceptin. 18 didn't, since they were enrolled before Herceptin became standard of care for HER2 3+. There were 108 vaccinated subjects in the study (HER2 1+, 2+ AND 3+). 12 HER2 3+ of 108 overall is 11.1%. Zero low HER2 expressing subjects receive Herceptin, because it isn't standard of care. In the studies subjects get standard of care, and must be disease free, as the protocol stipulates, beyond common sense.
    Alan, thanks for the great interview!
    Feb 4, 2014. 02:58 PM | 3 Likes Like |Link to Comment
  • Galena Biopharma: Numerous Red Flags Suggest A Significant Overvaluation [View article]
    I've read all of the abstracts, peer reviews, etc for NeuVax and AE37, and have discussed them with the actual investigators numerous times. I said "low HER2 expressing" subjects. 12 of 30 HER2 "3+" also known as "HER2-overxpressing" subjects received Herceptin. The studies started before Herceptin was standard of care, hence the HER2 3+ enrolled before 2006 didn't receive Herceptin. Herceptin is not standard of care for low HER2 expressing subjects, hence the HER2 1+ and 2+ subjects did not get Herceptin. 108 vaccinated subjects comprise the early NeuVax studies. 12 HER2 3+ subjects received Herceptin out of the 108 total (1+, 2+ and 3+). 12/08 = 0.11111. Times 100 = 11.1%.
    "Our trials began enrolling patients before trastuzumab became the standard of care therapy for HER2-overexpressing breast cancer in the adjuvant setting; therefore, the majority (68.8%) of patients with HER2-overexpressing tumors did not receive trastuzumab. Of 30 vaccinated patients who had HER2-everexpressing tumors, 12 patients received trastuzumab before vaccination..."
    12 of 30 HER2 3+, and 12 of 108 overall, or 11.1%.
    Cancer, Vol 118 Issue 10, 2594-2602

    Herceptin wasn't given to the low HER2 expressing subjects (vaccinated or control) in either the NeuVax or AE37 Phase II studies.
    Feb 3, 2014. 09:11 PM | 6 Likes Like |Link to Comment
  • Galena Biopharma: Numerous Red Flags Suggest A Significant Overvaluation [View article]
    Quote from the article: "A number of patients could have been enrolled in the study with disease that was "undetected". With such a small sub-group of patients; by chance, it is not that far-fetched to believe that the control group could have had subjects with undetectable disease that progressed further, possibly skewing the study results in favor of NeuVax. Therefore, we should rely on the overall study results of the data for all 188 patients enrolled in the study. This data is more likely to predict the outcome of the PRESENT Phase III trial. Let me remind you, NeuVax failed to show a meaningful benefit."
    I hope the patients in the peptide vaccine studies are paving the way towards a new future for immunotherapy, never mind feelings about a stock. The author of today's article delves into many topics while stating his position, and I enjoyed the read. I'll respectfully note that I disagree with the thoughts that I quoted above. Would it be equally fair for someone who is LONG $GALE to opine that the vaccine group could have had subjects with undetectable disease that progressed further, proving the efficacy of the vaccine? There is no scientific data to support either hypothesis, as it is simply an unproven suggestion.

    As stated in the same abstract which was presented at the ASCO Annual Meeting in 2010, "the only significant prognostic difference between the groups was more ER/PR negativity in the VG (p=0.04)." So, the only significant difference in the two groups (vaccine vs. control) favors a positive outcome for the control group. Also, the abstract notes that, "importantly, due to trial design, 72 patients received less then what was determined to be the optimal biologic dose." http://bit.ly/1j0rlxv

    Therefore, I have doubts "that we should rely on the overall study results of the data for all 188 patients enrolled in the study." Would the other 106 have had a better outcome if they received the optimal dose, never mind being included in a booster series that was added late to the studies, or if they had already identified the population that would most benefit from NeuVax (node positive, HER2 1+ or 2+)?

    From the article: "If NeuVax truly worked, why is the study aimed to treat patients who are already disease free?"

    A couple of weeks ago, I had an email exchange with MD Anderson's Dr. Mittendorf about peptide vaccines, specifically AE37 and E75. The difference in current research vs. previous failed efforts, beyond the AE37 novel Ii-key approach at unlocking a powerful long lasting cd4 t cell response, is using peptide vaccines in the proper setting. Past studies focused on metastatic disease. Her focus is the adjuvant setting after patients are rendered disease free with standard of care therapy. In the metastatic setting the tumor microenvironment is overly hostile to the immune system, inhibiting a response to a peptide vaccine. However, other strategies employing other immunoagents such as antibodies targeting checkpoint molecules combined with the peptide vaccines have her confident that the vaccines will someday be successful for metastatic.

    I quoted her response to me in an article about AE37 that Seeking Alpha published last week:

    "I think it's safe to say that I have significant enthusiasm for vaccines to include NeuVax and AE37. In order for these vaccines to be efficacious, I believe they need to be used in the appropriate setting; specifically, given to patients in the adjuvant setting after they have been rendered disease free with standard of care therapy, in order to prevent recurrence. If ongoing clinical trials such as the phase III PRESENT trial investigating NeuVax were to show that the vaccine is effective in the adjuvant setting, it would be paradigm changing. The vaccine wouldn't change our recommendations with respect to things we know work - surgery, chemotherapy and radiation - but it could be added on as an additional measure to prevent disease recurrence." http://bit.ly/1eI1sv9

    I'm more on the AE37 side, but I appreciate all that has been learned from the NeuVax studies, and the low recurrence rate even in the data for all 188 patients is remarkable, as data from the separate vaccine studies validate one another in certain ways, especially in targeting the adjuvant setting. For the sake of the patients, I hope all the vaccines pass their studies and oncologists can figure out which one best fits each patients in a targeted approach, which may ultimately include vaccine w/ Herceptin.
    Feb 1, 2014. 10:11 PM | 27 Likes Like |Link to Comment
  • Galena Biopharma: Numerous Red Flags Suggest A Significant Overvaluation [View article]
    Herceptin wasn't given to the low HER2 expressing subjects (vaccinated or control) in either the NeuVax or AE37 Phase II studies.
    Feb 1, 2014. 03:59 PM | 13 Likes Like |Link to Comment
  • Emerging Biotech Takes Aim At Preventing Recurrent Breast Cancer [View article]
    Table 2.

    "12" HER2 overexpressors (which are 3+) received Herceptin

    http://bit.ly/1gry7fp

    HER2 1+ and 2+ did NOT, since Herceptin isn't standard of care in this group. Also, only 12 of 30 3+ subjects received Herceptin, because Herceptin wasn't approved in the adjuvant setting when the bulk of the Phase II was taking place (pre 2006).

    "Our trials began enrolling patients before trastuzumab became the standard of care therapy for HER2-overexpressing breast cancer in the adjuvant setting; therefore, the majority (68.8%) of patients with HER2-overexpressing tumors did not receive trastuzumab."
    Jan 29, 2014. 05:15 PM | 1 Like Like |Link to Comment
  • Emerging Biotech Takes Aim At Preventing Recurrent Breast Cancer [View article]
    Herceptin is not an approved treatment for HER2 1+ or 2+ patients. Patients with low HER2 expression did not get Herceptin in either the AE37 or NeuVax studies, only 3+. During the conference call of scientific advisors that I participated on, Dr. Ian Krop, Dana Farber Cancer Institute, talked extensively about why it would be harder to conduct a Phase III study if HER2 3+ subjects were included; ie. Herceptin is standard of care, hence the study would require thousands of additional participants, since proving superiority to Herceptin is a long hill to climb.
    A study is underway to test Herceptin in 1+ and 2+ subjects, although that's obviously a different study which doesn't involve the peptide vaccines. NeuVax is being studied in combo with Herceptin, as is the GP2 vaccine, and separate work involving AE37 has been conducted.
    Jan 28, 2014. 06:44 PM | 1 Like Like |Link to Comment
  • Emerging Biotech Takes Aim At Preventing Recurrent Breast Cancer [View article]
    Hi aresstock. Yes, I saw that afterhours on Friday. That was expected. The 8K on Jan 14 stated,

    "Under the June 17, 2013 securities purchase agreement, for a period of up to one year, each investor may, in its sole determination, elect to purchase, in one or more purchases, additional units consisting of convertible preferred stock and warrants at a purchase price in the amount originally purchased by such investor (the ‘Greenshoe”). The units purchased in the Greenshoe will be identical to the units of convertible preferred stock and warrants originally issued pursuant to the Stock Purchase Agreement.....yada yada...The Company has agreed to file the registration statement within 45 days after closing and to use its best efforts to have the registration statement declared effective within 120 days after closing."

    The closing for the greenshoe was Jan 15, the S1 on Jan 24 was the registration statement, and the next step is for the SEC to declare the registration statement effective (within 120 days of the closing). This is what the CEO was referring to when he said,

    "as per the Form 8-K we filed with the SEC on January 15, we have taken in $800,000 from the sale of Series F Convertible Preferred Stock (pursuant to the exercise of additional investment rights from the financing in July of 2013)..."
    Jan 26, 2014. 09:31 PM | Likes Like |Link to Comment
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