Antares: Reiteration Of My Buy Recommendation [View article]
I quote from the investment thesis of my report.
"Antares is in a strong financial position to launch Otrexup and to develop its promising pipeline as it ended the first quarter with over $80 million of cash. I project a cash burn of $15 million in 2013. Adjusting for the anticipated launch expenses associated with Otrexup and the hiring of the new sales force, I project a burn rate of $10 million in 2014. If this is correct, the cash position at the end of 2014 would be $55 million. I see no need for financing in 2013 or 2014 and the Company could turn profitable in 2015."
Trius Therapeutics: New, Positive Dimension For Investment Outlook [View article]
I don't want to set the expectation that an acquisition is imminent. I can't judge how excited Cubist might be about the serial passage data and they also might want to take a wait and see approach. However, if or when Cubist decided to move, they could use stock, cash or a combination. All are viable options.
Neuralstem: Anticipating More Efficacy Data From ALS Trial And Update On New Clinical Trials [View article]
My understanding is that a trial date has not been set. I do not have the knowledge or intelligence to predict the outcome. Based on past experience, my guess is that the most reasonable worst case outcome for CUR would be paying a modest royalty until the patents expire. I think that the patents in question may have a relatively short amount of time until they expire. This is not an issue that I am spending a lot of time on.
Northwest Biotherapeutics: Moving DC Vax-L Rapidly Forward And Starting DC Vax Direct Trials [View article]
Here is comparable information on King's College.
The United Kingdom structural counterpart to Fraunhofer is a little different but provides the same end result. It starts King’s College Hospital and King’s College London which are sister institutions within the overarching Kings College Healthcare Partners. King’s College Hospital is one of the premier teaching hospitals in the UK and will participate in clinical trials while Kings College London will manufacture DCVax-L for the phase III trial.
King’s College Hospital is a venerable and conservative institution, at least on the administrative side. They wanted to establish a working relationship and gain confidence in Northwest and Cognate before announcing the collaboration. The beginning of the relationship dates to the same time as Fraunhofer, but was only announced on April 20, 2012.
The training of the King’s College London personnel to produce DCVax-L followed the same process as with Fraunhofer with one important difference. The UK regulatory system for living cell products is more streamlined than Germany. In the UK, King’s College London is already certified for the manufacture of a broad range of living cell products and this covers the manufacture of DCVax-L while Germany requires a separate certification for each product. Other requirements have to be met in regard to good manufacturing practice, but DCVax-L fits within the existing certification held by Kings College London. As with the Fraunhofer facility, this product can be shipped for clinical trials throughout the UK and Europe and also can be a backup for the US.
In the US, the first step in conducting a clinical trial is to get approval from the FDA. Then the trial sponsor approaches the ethics committees of institutions that will participate in the trial to gain their approval to conduct the trial. The process is reversed in the UK as the first step is to gain approval from the institutions and then gain regulatory approval. Northwest has already received ethics committee approval at Kings College Hospital, and the form of that approval makes it applicable nationwide. So, Northwest will not have to obtain other ethics committee approvals at each individual medical center after this. The remaining step is regulatory approval from the UK’s “FDA,” which is the MHRA. Northwest believes that King’s College Hospital could begin enrolling patients in August or September. The gating factor is the regulatory approval of the clinical trial by the MHRA.
Site selection in the UK will be different from that in the US and Germany. The National Health System has organized the leading teaching hospitals like Kings College Hospital into designated territories or catchment areas in performing sophisticated services like brain surgery. For example, King’s College Hospital serves some 4.5 million people. Additional sites will also cover catchment areas with populations in the millions. In addition to King’s College Hospital, Northwest will probably need to recruit six to eight similar institutions in the UK. The more dispersed GBM treatment systems in the US and Germany will require 40+ sites and 25+ respectively. Northwest anticipates announcing additional sites in the UK in the immediate future.
Northwest Biotherapeutics: Moving DC Vax-L Rapidly Forward And Starting DC Vax Direct Trials [View article]
Here is a section on Fraunhofer that I wrote a year ago in my initiation report.
There is no real comparable organization to Fraunhofer in the US. It has the prestige of the Mayo Clinic, M.D. Anderson or Sloan Kettering in the US even though it does not perform clinical activity or clinical trials. It is a research organization with 60 institutes spread throughout Germany and the world, each focusing on different fields of applied science; healthcare is just one segment. It employs around 18,000 people, mainly scientists and engineers, with an annual research budget of about €1.65 billion. It is owned by the government and 30% of its funding comes from government grants and 70% from contract work, usually for small emerging companies like Northwest. Its strategic objective is to be a leader in applied research through a flexible, autonomous and entrepreneurial approach to research projects.
Fraunhofer interacts with many small biotechnology firms in the course of determining what projects it will undertake. The Northwest relationship began with a presentation by Ms. Powers. As I discussed earlier later, Ms. Powers and her Toucan Funds are an impressive story of entrepreneurialism in pioneering the development of living cell products. Fraunhofer was impressed by the technology platform of Northwest, its product portfolio and particularly by the manufacturing expertise of Cognate BioServices.
Fraunhofer had not seen any small company or for that matter large company involved in so many INDs for living cell products as was the case with Northwest and Cognate. At the time the relationship was being formed, Cognate was just coming off a surprise, unscheduled inspection from the FDA which it passed with no findings; this impressed the detail oriented Germans. Fraunhofer was also impressed by the data Northwest had generated in GBM and prostate cancer and that it was in late stage trials with DCVax-L.
There is natural concern from US investors that if Northwest has such great technology, why is it a bulletin board company and why is it so financially strapped. Metrics like these that quickly turn off US investors were not an issue for Fraunhofer. They did their own due diligence and analysis of the technology, product portfolio and manufacturing and went on to forge a strong relationship which creates enormous value for Northwest.
The relationship has gone through several stages that have brought it to its current status. After the two companies decided to form the collaboration, there was a four month period of technology transfer and training of personnel. The clinical and manufacturing information given to Fraunhofer was extensive. This was followed by a 12 to 14 month process that has brought Fraunhofer to the point of having manufacturing certification that allows it to ship product for clinical trials in Germany and throughout Europe.
Fraunhofer charges its partners for the research done on projects and Northwest will pay for product produced for clinical trials. However, in the beginning of the partnership Fraunhofer billed only nominal amounts and even then delayed billing for the first four months in deference to the strained finances of Northwest. Cognate pays a nominal baseline charge to maintain space and infrastructure in Fraunhofer’s clean room facility and will pay for manufactured product; this is passed on dollar for dollar to Northwest. With this, Northwest was able to get a state of the art clean room facility which would have been an impossibility to accomplish on its own and did so without any capital cost and without the two years of time needed to develop, equip and validate a new clean room facility. From Fraunhofer’s standpoint, the manufacturing expertise transferred from Cognate is the key benefit.
The critical process of gaining manufacturing certification in Germany started with Fraunhofer personnel being trained on site in the Memphis facility of Cognate. In addition to learning standard operating procedures, the certification process requires qualifying reagent suppliers and assays used in manufacturing and keeping records in a nearly identical fashion as in the Memphis facility. German personnel participated in validation and practice runs in Memphis. Cognate continues to supervise operations in Germany in order to make sure that the production processes in the two facilities are as nearly identical as possible.
An additional key contribution of Fraunhofer was to identify a number of major medical centers and investigators in Germany that should be a part of the phase III trial and communicate to the medical centers and investigators that this trial is being supported by Fraunhofer. The Fraunhofer brand carries tremendous weight and respect. They have identified up to 30 such sites and the quality of the investigators is made apparent as the lead investigator in the German trial is Frau Shukart, the incoming chairperson of the German Neurosurgeon Association whose members will be performing the brain surgeries in the phase III trial. Fraunhofer was also helpful in obtaining a $5.2 million grant from the German government that is expected to fund up to half of the costs of performing the phase III trial in Germany.
The relationship with Fraunhofer provides all of the aspects that small companies seek in partnerships with big pharma. They provide a broad spectrum of necessary skills for manufacturing, clinical trial organization and regulatory expertise. Fraunhofer operates independent of the government. It carries more prestige and raises less suspicion with key academics needed to run the trial than a profit oriented big pharma partner based on an illustrious track record stretching back more than 60 years.
Fraunhofer went through a plant inspection by German regulators on June 12 and 13, 2012 in preparation for the phase III trial. There were no findings that require meaningful work. The regulatory authorities asked for certain assays and standard operating procedures to be developed in regard to the placebo. This information was sent to the agency in the last week of June and Fraunhofer is hopeful of receiving its manufacturing certification in the near future that could allow the clinical trial enrollment to start in September. The Fraunhofer produced product following manufacturing certification can be shipped anywhere in Europe and can probably act as a backup to Cognate in the US; the FDA might require an in vitro bridge study showing equivalency of Fraunhofer and Cognate produced product.
Northwest Biotherapeutics: Moving DC Vax-L Rapidly Forward And Starting DC Vax Direct Trials [View article]
Phase III trials in oncology do have a very high failure rate. There are many causes for this. They are often done in cancers that are not currently well treated, patients are in late stages of their cancer and have failed other drug therapies. For cancers that have approved therapy, the new drug is added to standard of care and then the combination is compared to standard of care. They have to show a differential benefit. The deck is stacked against new drugs. I think that the many failures in phase II or III are very often the result of the trial design and patient populations. I don't know the percentage, but your estimate that 65% of phase III trials fail seems low. Intuitively, I think is is higher. Anyway, there are going to be significantly more failures than successes. This is why the Feuerstein-Ratain rule works. It can ignore the fundamentals of any particular situation and rely on the probability that there will be more failures than successes. However, some trials do work and the economic returns are often spectacular. Each investor has to judge the risk reward of each situation. From my own standpoint, I tend to avoid companies that are developing chemotherapy and targeted therapies. However, dendritic cell vaccines have caught my attention.
Northwest Biotherapeutics: Moving DC Vax-L Rapidly Forward And Starting DC Vax Direct Trials [View article]
A. I am not aware of this paper. I will check.
B. Regulators have no one to hold them to a timetable. The major hospitals who will enroll patients are ready and manufacturing is ready when approval is gained. I don't know of a problem that the German regulators might have.
C. Remember this is a phase I trial and it is usually the case that a drug intended for solid tumors is tested in several types of solid tumors. The unusual thing is that the Company, assuming acceptable results in the phase I trial, has the approval to move directly into a 24 patient phase II trial. What DC Vax Direct has going for it is its safety profile. The dendritic cell vaccines appear to be very safe whereas chemotherapy drugs and targeted therapies usually have dose limiting side effects, which sometimes are life threatening. The FDA in these early stages of the trial is very focused on safety.
D. They are doing this trial in patients who are severely ill. Remember, they are inoperable and generally have a few months or so to live. It would be encouraging to see tumors shrinking or stabilizing in this patient population.
Neuralstem: Update On Phase I Trial Of Neural Stem Cells In ALS Is Encouraging [View article]
SmithOnStocks Opines On Stocks: May 19th Edition [View article]
SmithOnStocks Opines On Stocks: May 19th Edition [View article]
Antares: Reiteration Of My Buy Recommendation [View article]
Antares: Reiteration Of My Buy Recommendation [View article]
"Antares is in a strong financial position to launch Otrexup and to develop its promising pipeline as it ended the first quarter with over $80 million of cash. I project a cash burn of $15 million in 2013. Adjusting for the anticipated launch expenses associated with Otrexup and the hiring of the new sales force, I project a burn rate of $10 million in 2014. If this is correct, the cash position at the end of 2014 would be $55 million. I see no need for financing in 2013 or 2014 and the Company could turn profitable in 2015."
Trius Therapeutics: New, Positive Dimension For Investment Outlook [View article]
Repligen Promises To Be A Cash Flow Machine [View article]
Transcept: Throwing In The Towel On Intermezzo [View article]
Neuralstem: Anticipating More Efficacy Data From ALS Trial And Update On New Clinical Trials [View article]
Northwest Biotherapeutics: Moving DC Vax-L Rapidly Forward And Starting DC Vax Direct Trials [View article]
The United Kingdom structural counterpart to Fraunhofer is a little different but provides the same end result. It starts King’s College Hospital and King’s College London which are sister institutions within the overarching Kings College Healthcare Partners. King’s College Hospital is one of the premier teaching hospitals in the UK and will participate in clinical trials while Kings College London will manufacture DCVax-L for the phase III trial.
King’s College Hospital is a venerable and conservative institution, at least on the administrative side. They wanted to establish a working relationship and gain confidence in Northwest and Cognate before announcing the collaboration. The beginning of the relationship dates to the same time as Fraunhofer, but was only announced on April 20, 2012.
The training of the King’s College London personnel to produce DCVax-L followed the same process as with Fraunhofer with one important difference. The UK regulatory system for living cell products is more streamlined than Germany. In the UK, King’s College London is already certified for the manufacture of a broad range of living cell products and this covers the manufacture of DCVax-L while Germany requires a separate certification for each product. Other requirements have to be met in regard to good manufacturing practice, but DCVax-L fits within the existing certification held by Kings College London. As with the Fraunhofer facility, this product can be shipped for clinical trials throughout the UK and Europe and also can be a backup for the US.
In the US, the first step in conducting a clinical trial is to get approval from the FDA. Then the trial sponsor approaches the ethics committees of institutions that will participate in the trial to gain their approval to conduct the trial. The process is reversed in the UK as the first step is to gain approval from the institutions and then gain regulatory approval. Northwest has already received ethics committee approval at Kings College Hospital, and the form of that approval makes it applicable nationwide. So, Northwest will not have to obtain other ethics committee approvals at each individual medical center after this. The remaining step is regulatory approval from the UK’s “FDA,” which is the MHRA. Northwest believes that King’s College Hospital could begin enrolling patients in August or September. The gating factor is the regulatory approval of the clinical trial by the MHRA.
Site selection in the UK will be different from that in the US and Germany. The National Health System has organized the leading teaching hospitals like Kings College Hospital into designated territories or catchment areas in performing sophisticated services like brain surgery. For example, King’s College Hospital serves some 4.5 million people. Additional sites will also cover catchment areas with populations in the millions. In addition to King’s College Hospital, Northwest will probably need to recruit six to eight similar institutions in the UK. The more dispersed GBM treatment systems in the US and Germany will require 40+ sites and 25+ respectively. Northwest anticipates announcing additional sites in the UK in the immediate future.
Northwest Biotherapeutics: Moving DC Vax-L Rapidly Forward And Starting DC Vax Direct Trials [View article]
There is no real comparable organization to Fraunhofer in the US. It has the prestige of the Mayo Clinic, M.D. Anderson or Sloan Kettering in the US even though it does not perform clinical activity or clinical trials. It is a research organization with 60 institutes spread throughout Germany and the world, each focusing on different fields of applied science; healthcare is just one segment. It employs around 18,000 people, mainly scientists and engineers, with an annual research budget of about €1.65 billion. It is owned by the government and 30% of its funding comes from government grants and 70% from contract work, usually for small emerging companies like Northwest. Its strategic objective is to be a leader in applied research through a flexible, autonomous and entrepreneurial approach to research projects.
Fraunhofer interacts with many small biotechnology firms in the course of determining what projects it will undertake. The Northwest relationship began with a presentation by Ms. Powers. As I discussed earlier later, Ms. Powers and her Toucan Funds are an impressive story of entrepreneurialism in pioneering the development of living cell products. Fraunhofer was impressed by the technology platform of Northwest, its product portfolio and particularly by the manufacturing expertise of Cognate BioServices.
Fraunhofer had not seen any small company or for that matter large company involved in so many INDs for living cell products as was the case with Northwest and Cognate. At the time the relationship was being formed, Cognate was just coming off a surprise, unscheduled inspection from the FDA which it passed with no findings; this impressed the detail oriented Germans. Fraunhofer was also impressed by the data Northwest had generated in GBM and prostate cancer and that it was in late stage trials with DCVax-L.
There is natural concern from US investors that if Northwest has such great technology, why is it a bulletin board company and why is it so financially strapped. Metrics like these that quickly turn off US investors were not an issue for Fraunhofer. They did their own due diligence and analysis of the technology, product portfolio and manufacturing and went on to forge a strong relationship which creates enormous value for Northwest.
The relationship has gone through several stages that have brought it to its current status. After the two companies decided to form the collaboration, there was a four month period of technology transfer and training of personnel. The clinical and manufacturing information given to Fraunhofer was extensive. This was followed by a 12 to 14 month process that has brought Fraunhofer to the point of having manufacturing certification that allows it to ship product for clinical trials in Germany and throughout Europe.
Fraunhofer charges its partners for the research done on projects and Northwest will pay for product produced for clinical trials. However, in the beginning of the partnership Fraunhofer billed only nominal amounts and even then delayed billing for the first four months in deference to the strained finances of Northwest. Cognate pays a nominal baseline charge to maintain space and infrastructure in Fraunhofer’s clean room facility and will pay for manufactured product; this is passed on dollar for dollar to Northwest. With this, Northwest was able to get a state of the art clean room facility which would have been an impossibility to accomplish on its own and did so without any capital cost and without the two years of time needed to develop, equip and validate a new clean room facility. From Fraunhofer’s standpoint, the manufacturing expertise transferred from Cognate is the key benefit.
The critical process of gaining manufacturing certification in Germany started with Fraunhofer personnel being trained on site in the Memphis facility of Cognate. In addition to learning standard operating procedures, the certification process requires qualifying reagent suppliers and assays used in manufacturing and keeping records in a nearly identical fashion as in the Memphis facility. German personnel participated in validation and practice runs in Memphis. Cognate continues to supervise operations in Germany in order to make sure that the production processes in the two facilities are as nearly identical as possible.
An additional key contribution of Fraunhofer was to identify a number of major medical centers and investigators in Germany that should be a part of the phase III trial and communicate to the medical centers and investigators that this trial is being supported by Fraunhofer. The Fraunhofer brand carries tremendous weight and respect. They have identified up to 30 such sites and the quality of the investigators is made apparent as the lead investigator in the German trial is Frau Shukart, the incoming chairperson of the German Neurosurgeon Association whose members will be performing the brain surgeries in the phase III trial. Fraunhofer was also helpful in obtaining a $5.2 million grant from the German government that is expected to fund up to half of the costs of performing the phase III trial in Germany.
The relationship with Fraunhofer provides all of the aspects that small companies seek in partnerships with big pharma. They provide a broad spectrum of necessary skills for manufacturing, clinical trial organization and regulatory expertise. Fraunhofer operates independent of the government. It carries more prestige and raises less suspicion with key academics needed to run the trial than a profit oriented big pharma partner based on an illustrious track record stretching back more than 60 years.
Fraunhofer went through a plant inspection by German regulators on June 12 and 13, 2012 in preparation for the phase III trial. There were no findings that require meaningful work. The regulatory authorities asked for certain assays and standard operating procedures to be developed in regard to the placebo. This information was sent to the agency in the last week of June and Fraunhofer is hopeful of receiving its manufacturing certification in the near future that could allow the clinical trial enrollment to start in September. The Fraunhofer produced product following manufacturing certification can be shipped anywhere in Europe and can probably act as a backup to Cognate in the US; the FDA might require an in vitro bridge study showing equivalency of Fraunhofer and Cognate produced product.
Northwest Biotherapeutics: Moving DC Vax-L Rapidly Forward And Starting DC Vax Direct Trials [View article]
I meant to write that "I don't know the percentage, but your estimate that 65% of phase III trials succeed seems high.
Northwest Biotherapeutics: Moving DC Vax-L Rapidly Forward And Starting DC Vax Direct Trials [View article]
Northwest Biotherapeutics: Moving DC Vax-L Rapidly Forward And Starting DC Vax Direct Trials [View article]
http://bit.ly/13hprPx
Northwest Biotherapeutics: Moving DC Vax-L Rapidly Forward And Starting DC Vax Direct Trials [View article]
B. Regulators have no one to hold them to a timetable. The major hospitals who will enroll patients are ready and manufacturing is ready when approval is gained. I don't know of a problem that the German regulators might have.
C. Remember this is a phase I trial and it is usually the case that a drug intended for solid tumors is tested in several types of solid tumors. The unusual thing is that the Company, assuming acceptable results in the phase I trial, has the approval to move directly into a 24 patient phase II trial. What DC Vax Direct has going for it is its safety profile. The dendritic cell vaccines appear to be very safe whereas chemotherapy drugs and targeted therapies usually have dose limiting side effects, which sometimes are life threatening. The FDA in these early stages of the trial is very focused on safety.
D. They are doing this trial in patients who are severely ill. Remember, they are inoperable and generally have a few months or so to live. It would be encouraging to see tumors shrinking or stabilizing in this patient population.