Celsion Corporation (CLSN)

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CLSN: a lot of major near-term catalysts for higher PPS ahead: My PPS Target 2020: 5$; Here is why.
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The market obviously gives CLSN no credit for its development pipeline. This is due to the fact that CLSN's most important pipeline product – ThermoDox – had a major setback in its pivotal clinical trial 2013. But this is past history and the company has made great achievements with ThermoDox and GEN-1 and the risk:reward ratio has never been better IMHO.

Now the risk of missing out a big opportunity is high and a series of catalysts for a major increase of the company value and share price are just ahead and there is no Immediate need for further financing this year. Co’s statement: “We have a strong Balance Sheet Plus the Sale of New Jersey State Net Operating Losses Expected to Fund Operations into First Half of 2021”

2020 Near-term catalysts and PR news flow to occur down the road:
### GEN-1 (Ovariar Cancer) Phase II, Dosing of Dose Escalation Patient Portion finished – January 2020
### GEN-1 (Ovariar Cancer) Phase II, Site Activation (25 Clinical Trial Sites) finished – End of January 2020
### GEN-1 Surgical results and tumor response data from “Dose Escalation Portion” patients: will be available shortly thereafter (February – March 2020)
### GEN-1 Start of Dosing Phase II, 230 patients at 25 sites - (February – March 2020)
### ThermoDox (Liver Cancer) Optima Phase III study: Trigger for 2nd pre-specified interim efficacy analysis “158 events reached” – 2nd quarter 2020 (128 events were hit August, 2019)
### ThermoDox (Liver Cancer) Optima Phase III study: Data 2nd pre-specified interim efficacy analysis – April-June 2020 with potential for early halt und subsequent early NDA submission
### CLSN China Operations: Start of registration and operation of the new CLSN Subsidiary/ Facility in Hangzhou for liver cancer therapy market entry in China – several milestones planned for 2020
### CLSN China Operations: Potential for ThermoDox filing for approval in China – 2020

A series of news events is to expect in near future and to be continued in 2020. All these events have the potential to unlock the real pipeline and company value – because both advanced pipeline products (ThermoDox and GEN-1) address a billion $ market opportunity each - with an urgent need in their proposed indications. The ThermoDox registrational Phase III trial is a global trial – designed to support the approval in US, China and EU.

The company has a balance sheet which supports operations and trials until mid 2021 (company statement). The company can tap the opportunity of selling Net Operating Loss – a non dilutive measure.

Oppenheimer comments...
Celsion Corporation (CLSN) reported 4Q18 and provided a business update to investors last Friday. In focus, CLSN is approaching two interim analyses for ThermoDox from the fully-enrolled Phase 3 OPTIMA study expected in 3Q19 and 2020. We are encouraged by the DMC's December 18, 2018 assessment, highlighting a median PFS of 21.2 months as of the October 4th data cut-off. In addition, the earlier-stage OVATION II with GEN-1 continues to progress, enrolling patients for dose selection and safety. With 2018 year-end cash of $27.7 million, CLSN has ample runway to reach these meaningful potential value-creating catalysts, in our view. We remain bullish.

Emerging data from the recent literature indicates that the quality of the immune response as opposed to its absolute magnitude is what dictates SARS-CoV-2 viral clearance and recovery and that an ineffective or non-neutralizing enhanced antibody response might actually exacerbate disease. The first-generation COVID-19 vaccines were developed for rapid production and deployment and were not optimized for generating cellular responses that result in effective viral clearance. Though early data has indicated some of these vaccines to be over 95% effective, these first-generation vaccines were primarily designed to generate a strong antibody response and, while they have been shown to provide prophylactic protection against disease, the durability of this protection is currently unclear. The vast majority of these vaccines have been specifically developed to target the SARS-CoV-2 Spike (S) protein (antigen), though it is known that restricting a vaccine to a sole viral antigen creates selection pressure that can serve to facilitate the emergence of viral resistance. Indeed, even prior to full vaccine rollout, it has been observed that the S protein is a locus for rapid evolutionary and functional change as evidenced by the D614G, Y453F, 501Y.V2, and VUI-202012/01 mutations/deletions. This propensity for mutation of the S protein leads to future risk of efficacy reduction over time as these mutations accumulate.

Celsion’s next generation vaccine initiative stands at the confluence of immunotherapy and immunogenicity and envisions delivery, on a single plasmid, multiple SARS-CoV-2 antigens in conjunction with a potent immune modifier, interleukin-12 (IL-12), which directs a TH-1 immune response, stimulates T-cell immunity, and also promises the promotion of humoral immunity (antibody response). While most COVID-19 vaccines in late-stage clinical development are monovalent (S protein antigen only), Celsion has taken this multivalent approach in an effort to generate an even more robust immune response that not only results in a strong neutralizing antibody response, but also a more robust and durable T-cell response.

Celsion’s vaccine candidate approach comprises a single plasmid vector containing the DNA sequence encoding the cytokine IL-12 and multiple SARS-CoV-2 antigens, including S antigen in combination with the membrane (M) or nucleocapsid (N) antigen. Delivery will be evaluated intramuscularly, intradermally, or subcutaneously with a non-viral synthetic DNA delivery carrier that facilitates vector delivery into the cells of the injected tissue and has potential immune adjuvant properties. Unique designs and formulations of Celsion vaccine candidates offer several key advantages.
 

While the antibodies against S antigen would prevent virus entry into cells, the M and N antibodies could help virus clearance through antibody-mediated opsonization and phagocytosis. The presentation of multiple antigens on the cell surface of vaccine-injected tissue produces a broad variety of killer T-cells which could potentially produce more efficient viral clearance than a single antigen vaccine.

 

Since IL-12 is an essential regulator of the differentiation, proliferation, and maintenance of T helper 1 (TH-1) cells that generate killer T-cells and memory T-cells against virally infected cells, its simultaneous expression could boost the viral clearance by the vaccine and improve the immune system’s memory against any future exposure of the same virus.

 

Finally, the synthetic polymeric DNA carrier is an important component of the vaccine composition as it has the potential to facilitate the vaccine immunogenicity by improving vector delivery and, due to potential adjuvant properties, attract professional immune cells to the site of vaccine delivery.



Celsion’s PLACCINE DNA vaccine technology platform is characterized by a single multi-cistronic DNA plasmid vector expressing multiple pathogen antigens along with a potent immune modifier and delivered with a synthetic delivery system. It is easily adaptable to creating vaccines for a multitude of pathogens, including emerging pathogens leading to pandemics as well as infectious diseases that have yet to be effectively addressed with current vaccine technologies. This flexible vaccine platform is well supported by an already established supply chain to produce any plasmid vector and its assembly into a respective vaccine formulation.