Inovio Pharmaceuticals erwartet top line results

To add, the demonstrated efficacy in Phase I was exhibited without reaching the maximum tolerated dose. A more concentrated dose in future Phase II trials could potentially further raise efficacy. There are currently no approved treatments for lung cancer patients with the T790M mutation, which reverses the effect of the standard treatments of advanced NSCLC after failure of chemotherapy.

It's not hard to see why the price of CLVS has surged 130% in the last three months. The company saw a slight run up to the data release date on June 3rd and jumped more than two fold following the encouraging data. Its promising early stage success and the vast need for an approved treatment of NSCLC could fast track Clovis's drug with FDA Breakthrough Status, providing investors with additional value.

Inovio's shot to validate synthetic DNA vaccines

Inovio Pharmaceuticals is a development stage company that focuses on providing universal protection against cancers and various diseases through its synthetic vaccine technology and delivery process. Recent successful preclinical study announcements against viruses Ebola, Marburg and H7N9 validated its Syncon universal vaccine for influenza strains. With these vaccines and others in its pipeline, Inovio hopes to satisfy the vast need for a synthetic vaccine technology and, in turn, become the modern conventional preventive and therapeutic treatment of various diseases.

Current protection against influenza has shown weaknesses in the ability to react to rapidly changing strains, as the protective vaccine may not be the same as the common virus affecting people. Instead of guessing the target, INO combines DNA sequences from existing virus strains into a single dose to protest against multiple influenza strains. With the delivery of the company's proprietary electroporation system, the DNA vaccine assists the immune system by creating antibodies to protect against broad virus strains. INO is looking to build on its rolling momentum with upcoming catalysts that concentrate on other disease fields to expand the pipeline and add incremental shareholder value.

HIV vaccine PENNVAX-B data

With July approaching, investors are patiently waiting for the publication of PENNVAX-B data to validate what the company reported in Phase I trials back in early 2012.

As a therapeutic vaccine for HIV-positive volunteers, the vaccine generated significant (75%) antigen-specific T-cell responses paramount in clearing chronic viral infections. To compare, other DNA vaccines that were delivered without electroporation yielded poor overall T-cell immune responses.
In a preventive setting with uninfected patients, PENNVAX-B demonstrated best in class results with 89% of subjects generating T-cell response.
If the upcoming publication reaffirms PENNVAX-B with a best in class distinction, the stock price of INO will gain traction as results would validate the potency of the company's synthetic vaccine technology platform. This event could bring a similar intraday price increase that CLVS experienced with its data announcement. However, in the less likely case that results are not as promising, investors will be faced with an opportunity to add to their position at pulled back prices. Nonetheless, Inovio should be seeing an increase in coverage and exposure from the approaching publication date and participation at the 2013 OneMedForum investor conference. Publicity for such small-cap biotechs is always a plus.

VGX-3100: The therapeutic vaccine to treat cervical dysplasias and cancers?

Market Outlook

20 million Americans are currently infected with human papillomavirus (HPV), valuing the global HPV therapeutics market at a forecasted $4.2 billion by 2017 (CAGR of 6%), according to GlobalData estimates. This moderate growth rate is primarily attributed to a weak pipeline landscape as most drugs are in early stage clinical development, so they are going to make an impact after 2017. The HPV market is mainly dominated by preventive vaccines, such as FDA-approved Gardasil and Cervarix, which are only meant for immunity against HPV infection in non-infected individuals. Once a person has been diagnosed with the HPV infection, these vaccines are not able to prevent the development of cervical dysplasia and cancer. This presents the need for a novel first-in-class therapeutic vaccine to treat cervical dysplasia and cancer caused by HPV.

VGX-3100 Trials

VGX-3100 is a therapeutic DNA vaccine designed to treat cervical intraepithelial neoplasias (CIN) that are caused by human papillomavirus types 16 and 18. Inovio is in the process of enrolling females internationally for the Phase II clinical trial which is expected to have data ready by Q1 2014. The primary endpoint of this internally funded Phase II study is to assess the regression of cervical lesions and clearance of HPV 16 or 18. In other words, the company wants to further evaluate the efficacy and safety of the vaccine against the placebo in its attempt to treat cervical dysplasia and cancer patients.

Phase I results indicated that VGX-3100 has the potential to drive robust immune responses to antigens from high risk types of HPV infection as well as produce killer T-cells that destroy cervical dysplasia cells. The positive outcomes of the Phase I study achieved best-in-class immune responses which lay a strong foundation for the company to continue ongoing trials.

Although the Phase II data for VGX-3100 is still several months away, the cervical dysplasia vaccine is the most advanced independent therapeutic treatment in Inovio's pipeline. If all goes as planned, VGX-3100 may be INO's first commercialized product, providing the company with a consistent revenue stream. In addition, the vaccine would satisfy an immediate need in the HPV therapeutic market that has no successful treatment for infected individuals. If the Phase II results exhibit the same promising success as preceding Phase I VGX trials, Inovio would share similar traits to Clovis; promising early stage results for a difficult to treat disease that needs an approved treatment. As seen above, VGX-3100 could be Inovio's own CO-1686 by duplicating the recent surge in Clovis's value.

Insulation from several risks

Healthcare companies, especially pre-profit small-cap firms, are undoubtedly susceptible to risks that cause the subject company to flounder. With volatile biotechs, investors know there is a greater amount of speculation involved due to the wide array of vulnerability. I will be discussing three of the most common risks and suggesting how Inovio is well protected against them. This, however, should not encourage investors to disregard their own findings.

Financing Risk

On March 12th, 2013, the company closed an offering of approximately 27.4 million shares and warrants with net proceeds of roughly $14 million. With this financing, Inovio has cash, cash equivalents & short-term investments of $28.2 million, which is enough to fund the company through 2014. Additionally, many of the company's operations are funded externally by their wide array of partners. This financial assistance, through grants and contracts, minimizes Inovio's own out-of-pocket expenses when conducting costly clinical trials. Although it is inevitable that a development stage company like Inovio will raise capital through dilution, this risk is off the table for the foreseeable future.

Clinical Trial Risk

Inadequate results on the basis of not meeting efficacy or safety endpoints are the greatest risk factor for Inovio. The company's historical data and experienced staff mitigate this risk by providing overall positive results. Moreover, this risk is shared as the majority of Inovio clinical studies are conducted with a partner who may fund or collaborate on the trial. On the other hand, comparing the risk-to-upside ratio for these studies, positive results may potentially lead to licensing deals. In these events, INO may strike lucrative agreements, such as a further development with Merck or expanding its Asian network through VGX International.

Systematic Risk

The recent instability of global economies and talks of a market correction have made this risk a probable reality. Though this risk is out of investors' hands, the company's operations and financial position insulate it from any major global events. Performance of INO stock price is primarily driven by its own fundamentals and catalysts instead of economic factors such as The Fed's bond purchasing agenda. To add, the company sports a debtless balance sheet with current assets equaling nearly a quarter of market cap. Inovio's investments are held in liquid money market funds and their cash is sufficient enough to weather any storm within the next year.

Value Proposition

A recent report, "Global Vaccine Market Forecast to 2017", valued the 2012 global vaccine market at $27.3 billion. According to their findings, the market is expected to grow at a CAGR of around 12% until 2017, resulting in a $48 billion global market. By this time, it is expected that Inovio's VGX-3100 would be on the market, assuming no setbacks, and that several of its other pipeline candidates for HIV and Influenza would be at, or nearing Phase III trials.

Assuming the company is able to capture a conservative 0.25% of the vaccine market by 2017, it would lead to sales of $120 million. With further partnerships, greater royalties and a potential best in class therapeutic treatment for cervical dysplasia and cancer on the market, the projected 2017 sales figure is not out of reach. Trading at the industry average sales multiple of 9x would value the company at a market cap just north of $1 billion in 2017. A present valuation of $378 million is calculated if the 2017 figure is discounted with a rate of 35% for 3.5 years. This brief calculation is very sensitive to assumptions, but even with minor adjustments on the sensitivity table, the current company price illustrates enormous upside potential.

Conclusion

Inovio's diverse pipeline tailored towards difficult to treat diseases and cancers offers much promise for the future outlook of the company. Its successful track record of announcing potent treatment results during clinical trials bode well for upcoming catalysts such as the HIV data and VGX-3100 further down the road. Well-managed operations and financial stability secure the company against possible risks, which also validate the potential upside of Inovio at currently discounted pricing. Any potential for partnerships following positive results will add further value to investors' pockets as the company continues its epic year.

MFG
Chali

Inovio researchers constructed a consensus DNA vaccine targeting the HA influenza antigen based on sequences collected from several infected H7N9 patients to create a vaccine that is broadly protective against all H7N9 strains. Inovio's vaccine was administered in mice using its proprietary electroporation-based delivery technology twice, 3 weeks apart; the mice were then exposed to a lethal dose of A/Anhui/1/13 strain of H7N9 virus 4 weeks after the second vaccination. The challenge studies were conducted by Inovio's collaborators at Canada's National Microbiology Laboratory in Winnipeg. Results demonstrated that 100% of the vaccinated animals (n=10) remained healthy without any weight loss (a key indicator of health) and survived while all unvaccinated mice in the control group (n=10) had significant morbidity, including up to 30% weight loss, and died within 8 days of challenge.

This study showed for the first time that an H7N9 flu vaccine can protect against this newly emergent influenza subtype, with the added novelty that Inovio's newly created universal "construct" for this subtype was not matched to the virus strain, suggesting the potential to provide protection against other mutated strains that would be expected to emerge within the H7N9 family of influenza. These results also show the speed at which Inovio can construct and test a DNA vaccine against a new virus or new subtype of a virus.

Dr. J. Joseph Kim, Inovio's President and CEO, said, "We need truly preemptive, broad protection against multiple known and new strains within existing families of viruses. Furthermore, history has shown that new viruses and virus subtypes do periodically emerge − H7N9 being just one recent example − and speed in creating a new vaccine will be of the essence in pandemic situations. Inovio is proving its abilities on both counts. This new preclinical data further validates the power of Inovio's DNA vaccines to induce antigen-specific antibody and T-cell responses, which we have also demonstrated across other medical conditions such as pre-cancerous lesions and HIV."

Inovio previously reported that this newly developed H7N9 influenza DNA vaccine generated greater than 1:40 hemagglutination inhibition (HAI) titers in 100% of tested animals, with a geometric mean HAI titer of 1:130 against the A/Anhui/1/13 strain of H7N9 virus. This newly reported generation of strong T-cell immune responses tested by the ELISpot assay as well as the superb challenge data further demonstrates the power and potential of Inovio's universal flu vaccine franchise.

Using Inovio's synthetic consensus design approach the company has created universal DNA constructs for key virus clades (branches) within the Type A subtypes H1N1, H2N2, H3N2, and H5N1 as well as Type B. These constructs target multiple influenza antigens associated with influenza, including the most frequently changing antigen, HA. Inovio can mix and match these individual DNA plasmid constructs as desired to create vaccine candidates. Inovio has previously reported human data indicating protective immune responses against the subtypes H1N1 and H5N1.

MFG
Chali

Robust T-cell responses were generated in 89% of the subjects that received three vaccinations of PENNVAX-B, which consists of 1 mg of each of three DNA plasmids (encoding for HIV gag, pol, and env proteins) along with 1 mg of IL-12 DNA plasmid, followed by intramuscular electroporation with Inovio's CELLECTRA device. Three or four vaccinations with a 2 mg dose of each PENNVAX-B plasmid plus 1.5 mg of IL-12 DNA generated fewer responses when delivered without electroporation.

Comparative T-Cell Response Rates:

PENNVAX-B Plus DNA IL-12 With and Without CELLECTRA Electroporation (EP)

Regimen
CD4
CD8

Half dose, 3 vaccinations, with EP
80.8% (21/26)
51.9% (14/27)

Full dose, 3 vaccinations, without EP
19.2%   (5/26)
6.9%     (2/29)

Full dose, 4 vaccinations, without EP
40.7% (11/27)
3.6%     (1/28)


Notably, using only half the vaccine dose, and only three doses as compared to four, CELLECTRA electroporation generated a 45% point increase (7% to 52%) in the generation of CD8 T-cells compared to the subjects that received a full dose without electroporation. In the three-vaccination regimen with electroporation, 88.9% (24/27) of subjects developed a robust CD4 or CD8 response. Six months after vaccination, T-cell response rates remained strong and persistent in the subjects that received only three doses delivered by CELLECTRA EP. Of 24 positive CD4 or CD8 T-cell responders following the third and last vaccination in month 3, 79% (19/24) showed persistent CD4 or CD8 T-cell responses at month 9. There were no safety issues observed when Inovio's DNA vaccine for HIV was co-administered with IL-12 DNA and delivered using electroporation with CELLECTRA.

CD4 and CD8 T-cells are both important in cellular immunity, however, CD8 T-cells are considered especially integral to fighting cancers and chronic infectious diseases. Achieving a robust CD8 T-cell response in a significant number of patients, i.e. a significant response rate, has been a particular challenge for HIV researchers. In this study, PENNVAX-B generated CD8 T-cell responses with significant magnitude (as measured by the validated HVTN assay).

In other study arms that did not achieve statistical significance, the use of IL-12 DNA appeared to positively impact T-cell response rates. The increased response rate only occurred when IL-12 DNA was delivered with electroporation. This effect may be further investigated in future studies of Inovio DNA vaccines delivered with electroporation.

Dr. J. Joseph Kim, Inovio's President and CEO, said, "This is the second major scientific journal to publish clinical papers demonstrating our best-in-class T-cell responses from two of Inovio's product candidates in two different disease indications.

"This proof-of-concept data highlights not only the robust HIV-specific T-cell production achievable with next-generation vaccine technology, but clearly defines in a human comparison study the very significant impact of our CELLECTRA electroporation technology in increasing targeted immune responses – with a dose sparing benefit and excellent safety outcomes to date. The difference in T-cell generation is striking and will benefit the further development of our transformative DNA vaccines to treat and prevent HIV infection and other diseases. We have incorporated this knowledge from the single-clade PENNVAX-B program into the design of our multi-clade PENNVAX®-GP vaccine, which is now our lead preventive and therapeutic vaccine that broadly targets global HIV strains, and look forward to initiating our first human study of this vaccine later this year. PENNVAX-GP was developed through a $25 million contract with the NIAID; the clinical study of PENNVAX-GP will also be conducted by the HVTN."

Inovio's patented CELLECTRA electroporation delivery technology uses controlled, millisecond electrical pulses to create temporary pores in the cell membrane and allow significant cellular uptake of a synthetic DNA vaccine previously injected into muscle or skin. This technique has been shown to increase gene expression of the encoded "antigen" by as much as 1000-fold compared to vaccination without electroporation.

Inovio's cutting-edge DNA and electroporation technology also avoids issues that have plagued some other vaccine platforms: for example, researchers have observed that some vector-based vaccines may be associated with the lessening of immune responses driven by vaccination.

The two HIV phase I trials, HVTN 070 (without electroporation; n=120 patients); and 080 (with electroporation; n=48 patients); were multicenter, randomized, clinical trials. The studies were sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), an agency of the National Institutes of Health, and conducted by the NIAID-funded HIV Vaccine Trials Network (HVTN) at several clinical sites.

About the HVTN

The HIV Vaccine Trials Network (HVTN), headquartered at Fred Hutchinson Cancer Research Center in Seattle, Wash., is an international collaboration of scientists and educators searching for an effective and safe HIV vaccine. The HVTN's mission is to facilitate the process of testing preventive vaccines against HIV/AIDS. The HVTN conducts all phases of clinical trials, from evaluating experimental vaccines for safety and the ability to stimulate immune responses, to testing vaccine efficacy. Support for the HVTN comes from the National Institute of Allergy and Infectious Diseases (NIAID) of the U.S. National Institutes of Health (NIH). The Network's HIV Vaccine Trial Units are located at leading research institutions in 27 cities on four continents. Internationally renowned HIV vaccine and prevention researchers lead the units

MFG
Chali

July 10 - Inovio disclosed that its Cellectra device improved the effectiveness of its Pennvax-B HIV vaccine in a Phase I study. The study showed that Cellectra boosted the CD4 and CD8 T-cell responses for an increased number of patients.
How Is Inovio Succeeding?

The combination of data from Inovio over the last month also adds to the belief of many that its therapeutic approach does, in fact, work! While Phase I and preclinical trials are small, Inovio is trying to treat diseases and viruses that lack options-- meaning the regulatory path could be faster than normal if success continues to be shown.

Inovio's most advanced product is a Phase II vaccine, VGX-3100, to treat cervical dysplasia and cancer caused by HPV. The data is expected in the first quarter of 2014, and this data would completely support the therapeutic approach of this company.

Inovio is a company that has several early phase clinical and preclinical studies in the works. It currently has a market capitalization of $260 million, which you might think is too expensive, but let's not forget the market cap over $2 billion that Clovis has earned following early clinical data.

In my opinion, the stock has room to move higher and has stayed cheap for the mere fact that it uses an unorthodox approach, one that is rather confusing. For one, it is using synthetic vaccines that it manufactures, which isn't common among biotechnology companies in today's market. But most importantly, is the company's delivery technology, electroporation, which is being validated on Wall Street.

Electroporation is "how" Inovio's synthetic vaccines are delivered. The idea is that by using electroporation, many of the roadblocks that exist with drug delivery can be bypassed, and a better immune response can be observed.

According to Inovio, human cells are designed to resist the entry of foreign materials through the outer membrane, which is the primary challenge to achieving a powerful immune response. Therefore, Inovio's device uses electrical pulses to create a temporary pore in the cell membrane. Once these pores are created, anywhere in the body, Inovio can directly administer the vaccine to the targeted area. Due to bypassing the natural resistance of human cells, less of a vaccine is needed to produce a greater effect, and with fewer side effects.

If, in fact, Inovio's statement regarding human cells resisting foreign materials is accurate, then the idea of electroporation makes sense. After all, if you can overcome this defense roadblock and effectively direct a therapeutic to a particular area, then it seems obvious that a drug would be more effective. Hence, Inovio only has to produce an effective vaccine, and then its electroporation approach gives it an edge over the competition

MFG
Chali

Finding an effective therapy for PAD and CLI is imperative because the current standard of care relies primarily on palliative drugs and amputation. PAD affects 8 – 12 million Americans and is associated with a 20 – 30% risk of cardiovascular death within five years. CLI is a more severe stage of PAD affecting over one million people in the US. Up to 20% of CLI patients will die within 12 months of diagnosis; the five-year mortality rate exceeds 70%. The disease is characterized by ischemic rest pain—severe pain in the legs and feet while a person is not moving—or non-healing sores on the feet or legs as well as gangrene. Major limb amputation occurs in up to 40 – 50% of CLI patients within 12 months of diagnosis.

Dr. J. Joseph Kim, Inovio's president and CEO, said: "We have tremendous momentum and clinical data in achieving best-in-class immune responses with our SynCon® DNA vaccines delivered using our CELLECTRA electroporation system. Others have attempted to treat PAD using angiogenic growth factor DNA therapies without success. This study shows that combining our synthetic gene optimization techniques with our proprietary delivery systems could lead to an effective therapy. While early, this new application in treating PAD and other major chronic diseases offers Inovio a promising therapeutic avenue and additional commercial opportunity."

In this study, the gene sequence for HIF-1α was synthetically optimized to enhance expression of the growth factor. This DNA therapy was then delivered using Inovio's CELLECTRA constant current electroporation device, which has been shown to enhance the delivery of DNA plasmids by a 1000 fold using a millisecond pulse. A total of 39 mice were divided into 3 groups: (1) one group receiving HIF-1α DNA delivered with electroporation (EP) (n=13); (2) one group receiving HIF-1α DNA without EP (n=14) and (3) one group receiving a control empty plasmid (pVAX) delivered with EP (n=12). The left femoral artery in each mouse was tied up surgically to simulate an arterial blockage. The right legs were not treated and served as internal controls. The mice were then observed and scored for their limb function. Blood flow in their legs was measured by laser Doppler perfusion imaging.

The results demonstrated that EP delivery of synthetically optimized HIF-1α plasmid DNA significantly improved blood flow in the left hind legs and reduced necrosis (premature cell death) in a mouse model of hind limb ischemia when compared to the results from the two control groups. The treatment also improved survival from severe limb damage and amputation, reduced tissue damage, and increased the number of new capillaries and formation of larger collateral vessels

MFG
Chali

Dr. J. Joseph Kim, Inovio's president and CEO, said: "Inovio has demonstrated in multiple published human studies that our synthetically optimized DNA vaccines delivered with our CELLECTRA delivery system generate best-in-class T-cell immune responses. Here we show that in monkeys our hTERT DNA cancer vaccine generated T-cell immune responses more than 18-fold higher than the previous best results of a peer's hTERT therapeutic vaccine, which was also a DNA vaccine delivered with electroporation. We are particularly enthusiastic about our vaccine's potential use as a "universal" cancer therapeutic, given that hTERT is present in the vast majority of cancer types yet rare in normal cells. We plan to develop INO-1400 to treat breast and lung cancers and then expand to other cancer types. This hTERT therapy adds to a growing Inovio oncology franchise spearheaded by our phase II candidate, VGX-3100 for treating HPV-related pre-cancers and cancers, as well as our near clinical INO-5150 to treat prostate cancer."  

Data from both murine and human systems over the past 10 years have demonstrated that TERT-specific cytotoxic T-lymphocytes (CTLs) can recognize and kill TERT-expressing tumor cells in multiple types of cancers. In fact, previous research has shown that breast cancer patients who mounted an hTERT-specific CTL response exhibited significantly longer rates of survival. However, the immune system's tolerance of cancer cells and their associated antigens produced in the body, which exists to prevent autoimmune diseases, often restricts the immune system's antitumor response. A major challenge for cancer vaccine development has been to develop approaches to break this tolerance in tumor-bearing hosts. Recent advances in our understanding of antigen presentation and tolerance have led Inovio to create this synthetic DNA vaccine targeting the hTERT antigen.

Inovio constructed a highly optimized synthetic DNA vaccine with multiple proprietary features. Using its novel consensus design approach, two differentiating mutations were incorporated in the vaccine sequence to assist T-cells to more readily recognize self-made hTERT antigens and kill the cancer cells to which these antigens are attached (i.e. break tolerance). In addition, Inovio's use of a full length antigen DNA sequence encompasses multiple epitopes (parts of an antigen that are recognized by the immune system), potentially helping the immune system by providing multiple opportunities to overcome a tumor's ability to evade recognition by T-cells.

In the study, Inovio researchers confirmed that vaccination with Inovio's DNA vaccine delivered by adaptive electroporation induced hTERT-specific cellular immune responses with significantly greater T-cell magnitude compared to prior non-Inovio studies. Over four vaccinations there was a significant dose response, showing the value of multiple vaccinations to increase the immune response and highlighting the limitation of alternative technologies that are not amenable to multiple vaccinations such as viral vectors. Vaccination elicited multiple epitopes not only in mice, but also in monkeys, indicating a broad vaccine-induced immune response.

Study results showed that mice vaccinated with Inovio's DNA cancer vaccine and then challenged with a cancerous tumor experienced delayed tumor growth and longer overall survival compared with non-vaccinated mice. Mice first challenged with a tumor and then treated with the hTERT DNA vaccine displayed killing activity of the targeted cancer cells expressing the hTERT antigen, with no killing of normal cells that did not express the hTERT antigen. The treated mice experienced significantly smaller tumors and also longer overall survival. Vaccinated animal results were compared to a control group of animals that did not receive Inovio's DNA cancer vaccine.

In monkeys, whose TERT is 96% similar to human TERT and therefore a highly relevant model for immunotherapeutic vaccine development, the hTERT DNA vaccine elicited strong and broad TERT-specific immune responses and demonstrated the potential to eliminate tumor cells.

Overall, in these studies researchers observed that administration of a synthetic highly optimized hTERT DNA vaccine delivered with electroporation was capable of breaking immune tolerance, and eliciting robust and diverse antigen-specific CTLs, which are responsible for clearing cancerous cells, as well as a potent antitumor response. A favorable safety profile emerged from this study, showing that the vaccine-induced CTLs appeared not to be associated with any major toxicities or organ damage.

The expression of hTERT is thought to correlate with tumor survival and hTERT is associated with 85% of human tumors. Furthermore, there is growing recognition that it may be necessary to target stem cells that produce cancerous cells and recent studies have suggested that cancer stem or stem-like cells also express hTERT. These factors highlight the importance of an effective hTERT-targeting vaccine/immunotherapy and point to the potential benefit of Inovio's novel cancer vaccine

MFG
Chali

Merck's area of interest will presumably include a firm that's developed an immunotherapy platform, as this is the current treatment being used on oncology patients. The company may have several options: acquire a late stage pharma that has presented clinical benefits nearing commercialization, or propose a partnership deal with an early stage biotech oozing with potential. As Amgen's failed $10 billion bid for Onyx illustrated, the former can get quite costly. Its alternative is to partner with a development stage company that is able to provide a promising pipeline.

A flourishing and widely-held example to the riskier approach of partnering with an early stage biotech is the agreement between Johnson & Johnson and Pharmacyclics (PCYC). Back in December of 2011 when the collaboration was announced, the blood cancer drug, ibrutinib, was in Phase II of clinical trials. The agreement rewarded PCYC with as much as $1 billion. Now, almost 600% has been added to the $7.5 billion market cap of the once early stage Pharmacyclics. JNJ is fighting for the drug to receive breakthrough designation which would knock two years off the FDA process and get it one step closer to the market.

Merck is no stranger to premium acquisitions that have yet to prove themselves commercially. Back in 2006, to the surprise of many, Merck took a necessary gamble with early stage biotech Sirna Therapeutics by dishing $1.1 billion for the company (a 100% premium). Sirna's potential breakthrough RNA interference (RNAi) technology had just won the 2006 Nobel Prize in medicine as advocates believed it would be the basis of treatments for a wide swath of illnesses. Nonetheless, it was a very rich deal for a company that was years away from a commercial therapy. In hindsight, the purchase was a failed attempt for Merck, but it shows that the large pharma will place deep wagers if it believes the target has the prospective to become a blockbuster drug.

Inovio: Tailored for partnership with Merck

The 2013 summer has been quite sizzling for Inovio investors who have seen shares rally more than 105%. In the last month, the company has continued validating its therapeutic vaccines by consistently announcing strong T-cell responses during trials. Eager investors were banking on these catalysts to support the development of Inovio's proprietary technology platform that would guide the stock to levels it hadn't seen in years. The company did not disappoint as it is nearing three-year highs on the premise of a rejuvenated pipeline.

To summarize how Inovio got to current level:

On July 10th, Inovio announced the peer-reviewed publication of results from its phase I trials of PENNVAX-B preventive HIV vaccine, confirming what Inovio had found earlier with its 2012 studies. The journal reaffirmed PENNVAX-B with best in class distinction as Inovio's vaccine, together with the CELLECTRA device, significantly increased the number of responders producing robust and durable T-cell responses in humans. As expected, the street took the news very well with shares jumping 25%.

About a week after the HIV results, on July 18th, Inovio revealed a new application of its CELLECTRA electroporation technology. Animal studies showed an enhanced ability of DNA therapy to stimulate blood vessel growth and recover from debilitation caused by blocked arteries in the legs. While this is early in studies, this new application may be beneficial for treatment of peripheral arterial disease (PAD), offering Inovio another promising therapeutic avenue for commercial opportunity. Shares continued their upswing momentum by increasing 4% on the release.

Inovio added to its oncology franchise on July 24th when it announced preclinical studies for its hTERT DNA cancer vaccine, administered with CELLECTRA, generated robust immune response and in turn increased the rate of survival in mice and monkeys. Inovio's vaccine generated immune responses more than 18-fold higher than the next best hTERT therapeutic vaccine. High levels of hTERT are found in 85% of human cancers which allow Inovio to develop a widespread cancer therapeutic based on these early results. Inovio plans to advance its synthetic hTERT vaccine into clinical trials in 2014 by focusing on breast and lung cancers before expanding to other cancer types. Shares rallied 17% for two days following the exciting report.

Inovio's diverse pipeline passes over any downtime in company buzz which gives investors frequent future catalysts to look forward to. Come September, Inovio is presenting at three investor conferences across nation to continue increasing exposure and getting more investors to share their vision of revolutionizing vaccines. The 2013 agenda will include the phase I initiation of INO-5150 that targets prostate cancer while the first quarter of 2014 will bring the results of Inovio's phase II candidate, VGX-3100 for treating HPV-related cancers. Although the Phase II data for VGX-3100 is still several months away, the cervical dysplasia vaccine is the most advanced independent therapeutic treatment in Inovio's pipeline. If all goes as planned, VGX-3100 may be INO's first commercialized product, providing the company with a consistent revenue stream. These approaching events will provide channels of information for Inovio to continue driving momentum on its side.

Given Merck's dire need for a stimulant to its oncology division, collaboration with Inovio would be ideal. Inovio's growing oncology franchise would provide Merck with access to treatments of cancer that may potentially be blockbusters. Sharing global profits in such a deal would be an obvious advantage, similar to how JNJ is hoping to gain with their Pharmacyclics alliance. Partnering for an early stage cancer treatment, such as Inovio's robust hTERT therapeutic vaccine, may prove to be a strategic investment that rewards Merck shareholders handsomely while saving the company billions that would otherwise be expended on an acquisition.

For Inovio, partnering with a large pharma offers financial and experienced assistance in developing their early stage drug candidates. Delivered funding would cover costs and in turn reduce any pressures to dilute shareholders in order to subsidize development. Not to mention the validation and confidence Inovio would receive from the partnership with a global industry leader. To support this speculation, however, while presenting at the onemedplace conference, Inovio CEO Joseph Kim brought up that the company is currently in late stage discussions with a large pharma to bring a value changing partnership. Dr. Kim's connections to Merck, having been a senior vaccine developer, and Inovio's licensing agreement with the large pharma for its electroporation technology in 2004 give good indication that the two may be nearing an agreement to work together again.

Conclusion

A looming partnership provides Inovio shareholders with a worthwhile catalyst that will carry on the recent momentum seen with its share price. Merck's need to restore its oncology division and the connections with Inovio make the potential partnership more than a speculative desire. Even if Inovio's partnership discussions are not with Merck, the company's sizzling summer is expected to continue.

MFG
Chali

GW Bierro ebenso !!