INGN's fans will have to wait until Thursday for Dr. Sobol's presentation in Frisco, but now that many people were surprised by the fact that the Indians were able to defeat the
formerly mighty Yankees, it is probably about time that the shorts on INGN should start thinking about covering their position, in spite of the predictions of INGN’s demise by the now also formerly accurate prognosticator Adam Feurstein & his somewhat famous “Left Handed Biomarker”.<g>
INGN seems to be getting closer to deliver the first gene therapy approved for cancer in the United States.They expect the completion of regulatory filings in both the U.S. and EU by the end of 2007 & the designation of a marketing partner for Advexin.
Some things that the shorts should consider about Advexin:
Sibiono has been using the recombinant human Ad-p53 Injection, trademarked as Gendicine, for several Yrs. & cancer patients have been traveling to China,spending $20,000 to receive that treatment.
sibiono.com.
The endpoints of the ongoing PIII are tumor response and overall survival, which includes the evaluation of prognostic biomarker defined populations.
There are over 200 patients enrolled in the study “Advexin vs. Methotrexate , Clear Correlation Between P53 Biomarker and Survival”, & although Advexin probably could gain approval without biomarker analyses, based on its efficacy and strong safety profile, the biomarker data accumulated to date strengthens the case for use in other tumor indications.
The data for the p53 biomarker levels in the PII head and neck cancer study, in a relatively small patient population, showed a direct correlation with abnormal p53 levels and survival, with highly statistically significant results.
Abnormal overexpression of p53 protein (>20%),as detected by immunohistochemistry,was observed in 61% of the head and neck tumors tested, reflecting the abnormal p53 molecular signaling pathway targeted by p53 gene therapy. The percentage of p53tumors in Introgen’s study was consistent with the reported head and neck cancer in the literature.
Abnormal p53 overexpression was a predictive biomarker of Advexin efficacy in patients with recurrent, locally advanced head and neck cancer, as demonstrated by correlations with both tumor response (locoregional disease control) & increased median survival.
Advexin & Radiation combo:
Introgen's Advexin therapy has been evaluated in combination with radiation therapy in several studies for cancer.
In one PII study treating patients with non-small cell lung cancer approximately 60% of patients' primary tumors regressed or disappeared after the combination therapy, as assessed by both biopsies and by x-ray three months after treatment.
Additionally, Advexin therapy did not appear to increase the side effects caused by radiation treatment.
The results from those INGN's previous studies suggest that Advexin therapy may enhance the effect of radiation at local tumor sites without significantly increasing toxicity, according to Dr. Sobol. Approximately 715,000 cancer patients receive radiation therapy annually.
Introgen also controls numerous issued patents covering Advexin including the use of p53 for used alone and in combination with chemotherapy and radiation therapy.
Virtually all cancer patients receive chemotherapy or radiotherapy as part of standard cancer treatment.
Also the shorts apparently mistakenly associated INGN with the recent reports about the unfortunate event in which a patient experienced a serious adverse event and subsequently died while on a P1/2 of an investigational gene therapy for the treatment of inflammatory arthritis.
The FDA placed on hold that trial, which utilized a recombinant adeno-associated virus derived vector and delivers the gene for Tumor-Necrosis Factor –Receptor (TNFa).
None of Introgen’s product candidates nor technologies use adeno-associated virus or TNFa, which are characteristic of the biotechnology company’s recently halted clinical program.
INGN’s programs and technologies are not associated nor affected by that situation, its investigational therapies have been the subject of more than 30 clinical trials in 10 oncology indications involving approximately 700 patients.
No Introgen trial has ever been halted nor placed on hold by the FDA or any other regulatory authority. Introgen is proud of the high safety index that distinguishes its product candidates.
introgen.com
Also, what seems to be a promising pipeline, apparently receives little to no value. <g>
Besides ADVEXIN, INGN has:
INGN 241- mda-7; INGN 225 - p53 immunotherapy; INGN 401- nanoparticle formulation FUS-1; INGN 234 - p53 topical; INGN 402 - nanoparticle formulation p53;INGN 403- nanoparticle formulation mda-7 & INGN 007 - oncolytic viral therapy.
Note for the shorts:This last one doesn’t have any relation to the also formerly famous British agent.<g>
INGN 241 uses the mda-7 gene, a tumor suppressor that induces apoptosis, in many types of cancer.
The protein produced by the mda-7 gene is secreted and may also stimulate the body's immune system to kill metastatic tumor cells and to protect the body against cancer,it acts as a cytokine & is also known as interleukin-24, or IL-24.
It may attack cancer using two different mechanisms.
It is on a PIII, combined with radiation therapy, for head & neck Ca.s
On a PII for melanoma & solid tumor Ca.s
And on preclinical tests for breast & pancreas Ca.s
For INGN 241 use in combination with Velcade, Avastin & other, see previous note from Tuck as well as :
Message 23891653
INGN 225 uses the p53 tumor suppressor in a different manner than ADVEXIN to create a molecular immunotherapy for cancer that stimulates a particular type of immune system cell known as a dendritic cell. The immune system can recognize and kill tumors after treatment with dendritic cells stimulated by the p53 tumor suppressor, which suggests this therapy could have broad utility as a treatment for solid tumors. INGN 225 may also sensitize tumors to the effects of platinum and taxane chemotherapies. It is on PIIs for treatment of SCL & breast Ca.s
INGN 401 is a nanoparticle formulation FUS1, which is in P1-2 for metastatic, non-small cell lung cancer.
The FUS1 tumor suppressor is associated with the early onset of cancers & INGN 401 uses a nanoparticle vector to deliver FUS-1
Studies have shown that nanoparticle FUS-1significantly inhibits the growth of tumors and greatly reduces the metastatic spread of lung cancer in animals.
FUS1 expression has been detected in various normal human tissues, including brain, heart, pancreas, prostate, kidney, and lung, based on quantification of expressed sequence tags
On the basis of both the lung-cancer-growth-suppressing properties of the Fus1 protein in vitro and in animal models & the observed loss of protein expression in primary tumors & tumor-derived cell lines, it has been hypothesized that FUS1 would have to act as a TSG in a haploinsufficient manner because most primary lung cancers experienced allelic loss in this 3p21.3 region & that both loss of expression and deficient posttranslational modification of Fus1 protein might lead to loss of its tumor suppression function & to lung cancer development.
The functional domains of Fus1 protein showed a potential myristoylation site at the NH2 terminus, a protein kinase A interaction site, an A kinase-anchoring protein interaction (protein/protein) site, and a PDZ class II domain (Fig. 1A). From analytical comparisons of Fus1 protein structure and function, it was predicted that Fus1 is a myristoylated member of the cAMP-dependent protein kinase A & A kinase-anchoring protein families, which are associated with many cellular processes, including transcription, signal transduction, metabolism, ion channel regulation, cell cycle progression, and apoptosis.
Myristoylation Is Required for Fus1-Mediated Tumor-Suppressing Activities in Vitro and in Vivo.
cancerres.aacrjournals.org
INGN 234 is a mouthwash formulation of INGN’s p53 tumor suppressor therapy and is being tested for the prevention of oral cancers and the treatment of oral leukoplakia.
CL is collaborating with INGN on that subject & CL reportedly owns about 9% of INGN.Colgate has said that it made the investment to reinforce its position in oral health.
lexdon.com
INGN 402 is a nanoparticle formulation p53, which is in advanced pre-clinical testing and has demonstrated a good safety profile with promising anti-cancer activity in animal studies.
INGN 403 is a nanoparticle formulation mda-7, which is in preclinical studies. It is in pre-clinical studies & has demonstrated a good safety profile and promising anti-cancer activity in animal studies against various Ca.s
INGN 007 is a replication-competent viral therapy, which is also called an oncolytic virus, in which viruses bind directly to cancer cells, replicate in those cells, and cause those cancer cells to die.It is in preclinical studies & tests in animal models indicate that INGN 007 over-expresses a molecule that allows the vector to saturate the entire tumor. This tests have demonstrated that INGN 007 has a favorable safety profile and significantly inhibits tumor growth.
(Again, INGN 007 has no connection with the British secret agent.<g>)
Also to be taken into account is INGN 8.3% stake in SR Pharma, a British biotech firm quoted on the Alternative Investment Market.
At last report, the short position was still > 40x INGN’s ADV. (It seems that Adam Feuerstein et Al., will have to come with a better biomarker than his now already famous “Left Handed”. <G> )
Bernard |
