Company Profile

Regulon, Inc (Regulon) is a biopharmaceutical company committed to the discovery, development, testing, and commercialization of low toxicity anti-cancer pharmaceuticals based on a unique patented encapsulation technology.

Our objective is to develop a broad range of drugs to be used in cancer therapy. We believe we have achieved a breakthrough in the development of a unique liposome encapsulation technology.

Regulon engages in the discovery and development of nanopharmaceutics in oncology based on liposome encapsulation platform technology. Its products include Lipoplatin, a liposomally encapsulated cisplatin for various cancer indications, including non-small cell lung cancer and pancreatic cancer.

The company was founded in 1997 and is based in Athens, Greece & California with operations in Europe and Asia.

Regulon's unique liposome encapsulation technology applicable to drugs, small molecules, peptides, proteins and viruses, significantly reduces the side effects of chemotherapy known to exacerbate the quality of life (QOL) of cancer patients. The firm has successfully applied this technology to encapsulate two members of the platinum family of anticancer drugs: cisplatin and oxaliplatin.

Technology

One approach that has gained much attention in molecular biology is the development of liposome formulations that can be used for the encapsulation of drugs and other molecules for delivery to an organism.

Regulon has developed a unique liposome encapsulation technology applicable to drugs, small molecules, peptides, proteins, and viruses.

Lipoplatin™

Lipoplatin nanoparticles, loaded with cisplatin are uptaken by tumors and metastases (10 to 200-fold higher than normal tissue) by leaking through the compromised endothelium of tumor vasculature sprouted during neoangiogenesis, a process known as extravasation, and by the avidity of tumors for nutrients with Lipoplatin disguised as a nutrient with its lipid shell.

Moreover, Lipoplatin nanoparticles fuse with the cell membrane or are rapidly uptaken by cancer cells thus emptying their toxic payload inside tumor cells.

Additional Information

Technology

In order to overcome inefficient drug delivery, one of the major obstacles associated with efficient cancer therapy, Regulon, Inc. has developed a unique liposome encapsulation technology applicable to drugs, small molecules, peptides, proteins, and viruses.

Effective passive tumor targeting

Drug encapsulation takes advantage of chemical structural characteristics of various drugs especially those used for chemotherapy on cancer patients. Lipoplatin, the liposomally encapsulated form of cisplatin, brings a major breakthrough in molecular medicine reducing significantly the toxicity of cisplatin and enhancing its tumor targeting after intravenous injection to animal models implanted with human cancers. The encapsulation efficiency reaches extremely high yields unlike any other similar technology.

Passive delivery to tumors is achieved secretly from immune cells and normal tissues by encapsulation of the cytotoxic drugs into a natural lipid capsule protected with a PEG polymer; the 110-nm liposome nanoparticles exploit the compromised endothelium of tumor vasculature for their preferential extravasation to tumors and metastases. Lipids, composing the nanoparticle shell, are natural products, one of the four classes of biomacromolecules, compatible with the lipids of the cell membrane, unlike synthetic polymers used in other nanotechnology capsules with dubious cumulative toxicities.

Figure 1. The scheme shows the PEGylated liposome that is the carrier of the toxic drug cisplatin with its long-circulating properties in body fluids after intravenous administration.

Regulon’s nanoparticles carrying therapeutic drugs have long circulating properties in body fluids (Figure 1); this longevity in circulation is required for passively identifying the tumors and metastases in the body for their preferential targeting and extravasation in tumors. This preferential targeting of cancer tissue takes advantage of the imperfections in the vasculature sprouted by tumors to accelerate their growth during neoangiogenesis; the arteries, veins and micro-vessels in normal tissue have endothelial walls more compact compared to the “leaky” vasculature of tumors; as a result, tumors uptake 10- to 200-times more Lipoplatin nanoparticles than normal tissue.(Figure 2)

Figure 2. The scheme shows a blood vessel in tumor tissue. Lipoplatin nanoparticles of 100nm in diameter are depicted as spheres with the yellow toxic payload of cisplatin inside them. In normal tissue, blood vessels are impenetrable by small nanoparticles. On the contrary, tumor blood vessels have imperfections (tiny holes) in their walls (called endothelium); tumor blood vessels are established during the process of neo-angiogenesis (meaning sprouting of new blood vessels by a tumor cell mass during its growth phase). Lipoplatin nanoparticles take advantage of these tiny holes to pass through and extravasate inside the tumor reaching a concentration that can be 10- to 200-fold higher compared to the adjacent normal tissue.

This was demonstrated in human studies where patients were infused with Lipoplatin and the platinum levels were measured in surgical specimens from primary or metastatic tumors and the adjacent normal tissue. Regulon’s anticancer treatment minimizes the side effects of classic chemotherapy. In simple terms all primary tumors and metastases are being targeted regardless of the tumor type or size following intravenous administration of our drug. Their targeting depends primarily on the degree of tumor vascularization. Tumors of the stomach and breast for example have the highest degree of vascularization and are expected to accumulate more platinum drug after intravenous administration.

Crossing of the cell membrane barrier

Figure 3. Delivery of cisplatin “payload” directly to tumor cells facilitated by DPPG fusion circumventing the need for Ctr1-receptor mediated transportation required by naked cisplatin. After concentrating in tumors and metastases DPPG promotes the fusion of Lipoplatin with the cell membrane. Once they reach the tumor target Lipoplatin nanoparticles have the advantage, unique to Regulon’s technology, to fuse with the cell membrane of the tumor cell and empty their toxic payload inside the cytoplasm. Liposomes developed by others (e..g. Doxil of SPI-77 of Alza/J&J) are unable to do the fusion process; thus the toxic drug is emptied outside the tumor cell and is less effective.

Lipoplatin nanoparticles leading to delivery of their toxic payload inside the cytoplasm of the tumor cell where it is needed for anticancer efficacy (Figure 3). This is a major advantage in the implementation of the treatment in the clinic to enhance efficacy and eliminate toxicity. Crossing of the cell membrane barrier by Lipoplatin was also demonstrated in cell cultures (Figure 4).

Figure 4. Demonstration of the fusion or uptake of Lipoplatin nanoparticles using cancer cell cultures. The green donut-like structures are single cancer cells; their periphery where the cell mebrane is located fluoresces because it has uptaken fluorescent Lipoplatin nanoparticles or Regulon’s fusogenic liposomes as a control. Lipoplatin or DPPG-liposomes with fluorescent lipids enter rapidly MCF-7 human breast cancer cells thus providing proof of concept of membrane fusion or endocytosis to deliver the toxic cisplatin inside the tumor cell.

Synergy with radiation for tumor cell killing

Lipoplatin is the only nanoparticle drug available that contains a heavy metal inside a liposome. Platinum can uptake high energy from external sources such as laser or gamma rays that can burst the nanoparticle to release the toxic drug or to heat up the surrounding cytoplasm. These exciting properties are under current investigation to explore the full potential of this exciting nanoparticle.

Antiangiogenesis properties

Figure 5. Encapsulation of the beta-galactosidase gene into a liposome of the same composition as the Lipoplatin and systemic delivery to SCID mice with human tumors stained preferentially the vasculature that was developed by the tumors under the skin of the animals to supply the tumor with nutrients. From Boulikas T Molecular mechanisms of cisplatin and its liposomally encapsulated form, Lipoplatin: Lipoplatin™ as a chemotherapy and antiangiogenesis drug. Cancer Therapy Vol 5, 349-376, 2007

Antimetastasis potential of Lipoplatin

The antiangiogenesis property of Lipoplatin has been suggested from the encapsulation of the beta-galactosidase gene into a liposome of the same composition as the Lipoplatin liposome; after systemic delivery to SCID mice with human tumors (Figure 5) the foreign “blue” gene stained preferentially the vasculature that the tumors under the skin of the animals developed to supply the tumor with nutrients. This shows that Regulon’s liposomes can target preferentially the vascular endothelial cells; in case of Lipoplatin, targeting of these cells with toxic cisplatin instead of the “blue” gene would cause their destruction. Thus, Lipoplatin limits tumor vascularization by attacking their endothelial cells in addition to the known property of cisplatin to attack the epithelial cell of the tumor.

The antimetastasis potential of Lipoplatin was shown in a study from the “Reference Oncology Center, Italian National Cancer Institute” in Aviano. Lipoplatin inhibited both migration and invasion of cervical cancer cells supporting its antimetastasis potential. This is a very important feature of Lipoplatin because migration and invasion are essential steps used by cancers to mediate their metastases.

In a paper that appeared in September 2013 in “Gynecologic Oncology” (http://www.ncbi.nlm.nih.gov/pubmed/24029417), the investigators, led by Dr. Donatella Aldinucci have examined the effectiveness of Lipoplatin in cisplatin-resistant cervical cancer cells. In the Aldinucci study, Lipoplatin was effective in both cervical cancer and cisplatin-resistant cervical cancer cells thus opening the possibility to apply Lipoplatin successfully against cervical cancer both as first and second-line. Furthermore, the same study has elucidated novel mechanisms on how Lipoplatin kills cervical cancer cells:

  1. Lipoplatin treatment induced apoptosis in these cells, as evaluated by Annexin-V staining and DNA fragmentation, caspases 9 and 3 activation, Bcl-2, Bcl-xL down-regulation, and Bax up-regulation.
  2. Lipoplatin inhibited the activity of Thioredoxin reductase (TrxR) in cervical cancer cells. TrxR is a selenoenzyme which is over-expressed in many tumor cells and contributes to drug resistance; this finding revealed one of the several mechanisms Lipoplatin can kill cells resistant to platinum.
  3. Lipoplatin induced an increase in Reactive Oxygen Species (ROS) even in the presence of the ROS scavenger N-Acetylcysteine (NAC). This is an additional mechanism for mediating tumor cell killing by Lipoplatin.
  4. Lipoplatin reduced the expression of EGFR (epidermal growth factor receptor) and its phosphorylated form. EGFR is overexpressed in many tumor cells and thus the reduction of EGFR molecules on the cell membrane by Lipoplatin would have a strong anticancer effect.
  5. Lipoplatin inhibited both migration and invasion of cervical cancer cells. This is a very important feature of Lipoplatin because migration and invasion are essential steps used by cancers to mediate their metastases; over 90% of cancer patients succumb because of complications from metastases rather than the primary tumor.

Regulon’s liposome encapsulation technology can be applied to most of the 1,000 FDA approved drugs, thus increasing the Company’s fundamental value.

Lipoplatin™

The clinical development of Lipoplatin™ started in 2001. Lipoplatin™ is the liposome encapsulated form of Cisplatin. Cisplatin is one of the most widely used and most effective cytotoxic agents in the treatment of epithelial malignancies such as lung, head & neck, ovarian, bladder and testicular cancers. The continued clinical use is impeded by its severe adverse reactions including renal toxicity, gastrointestinal toxicity, peripheral neuropathy, asthenia, ototoxicity and optic neuropathy. However, Human studies have shown a different pharmacokinetic and biodistribution profile to that of cisplatin with serum longevity, a prelude to the extravasation and tumor invasion process by Lipoplatin™ nanoparticles.

Regulon has achieved a significant improvement (>90%), in the encapsulation of Cisplatin and has developed a reproducible manufacturing procedure.

Lipoplatin™ has the following advantages compared to administration of Cisplatin:

  • Significant reduction in overall systemic toxicity compared to Cisplatin, which means that higher concentrations can be administered allowing use of higher drug doses, more safely and more frequently.
  • Protection of the drug from rapid immune-system elimination.
  • Indications that the encapsulated drug crosses the blood-brain barrier.
  • Lipoplatin™ stays in circulation for extended periods of time and the Cisplatin is slowly released
  • Lipoplatin™ can selectively target tissues with altered vascularization, therefore targeting primary tumors and metastases; this reduces the overall toxic effect on normal tissue
  • The encapsulation technology seems to protect delivered compounds against host cell immune elimination responses.

Total platinum levels in plasma were dose-dependent and a half-life of 40-120 h was estimated for total platinum in sera of patients compared to 6h for cisplatin. Its urine excretion was also much slower and about 40% of the dose was excreted in the urine in 3 days compared again to ~8h for 50% excretion for cisplatin.

Additional studies on patients who underwent Lipoplatin infusion followed by prescheduled surgery have demonstrated a 10- to 200-fold higher accumulation in primary tumors and in metastases compared to the adjacent normal tissue. These are exciting results establishing Lipoplatin and Regulon’s liposome technology as a means to achieve high targeting. Even micrometastases, invisible in chest x-rays or CT scans, were proposed to be targeted by Lipoplatin because of the microvasculature sprouting in progress. The nanoparticle drug was inferred to target endothelial cells in tumor vasculature and its antioangiogenesis potential was proposed in addition to the classical chemotherapy activity.

Overall, Lipoplatin has proven to be a safe drug, the main toxicity being myelotoxicity. A Phase I study, where Lipoplatin was used as monotherapy, failed to reach the MTD. When used in combination with Gemcitabine, the dose of 120 mg/m2 was defined as MTD; higher doses were associated with increased myelotoxicity. A subsequent Phase I study determined the DLT for Lipoplatin monotherapy at 350 mg/m2 and the MTD at 300 mg/m2. For Lipoplatin-paclitaxel combination therapy, the DLT was 250 mg/m2for Lipoplatin and 175 mg/m2 for paclitaxel whereas the MTD was 200 mg/m2 for Lipoplatin and 175 mg/m2 for paclitaxel: Stathopoulos et al, 2010, Anticancer Res 30, 1317-1322

In a Phase II randomized comparative study on the efficacy and toxicity of 120 mg/m2 D1,8,15 Lipoplatin in combination with 1,000 mg/m2 gemcitabine D1,8 compared to 100 mg/m2 cisplatin D1 with same schedule of gemcitabine as first-line against NSCLC there were statistically significant less toxicities in the Lipoplatin arm and a better efficacy profile, especially in the non-squamous histological subtype. This schedule was promoted into a randomized Phase III study and an interim report showed statistically significant reduction in nephrotoxicity, asthenia, and neurotoxicity and enhanced efficacy in NSCLC adenocarcinoma.

The results of a different randomized comparative Phase III study on the efficacy and toxicity of Lipoplatin 200 mg/m2 D1 in combination with paclitaxel 135 mg/m2 D1 in a 14-day schedule compared to cisplatin 75 mg/m2 D1 with paclitaxel 135 mg/m2 D1 as first-line against NSCLC were reported with 114 and 115 patients in each arm. The study (see 9.12) demonstrated a statistically significant reduction in nephrotoxicity (6.1% vs 40%), and also a reduction of most other adverse effects including anemia, neutropenia and asthenia. The efficacy results established the noninferiority of Lipoplatin compared to cisplatin.

In a Phase II trial the toxicity and efficacy of Lipoplatin 120 mg/m2 D1,8,15 in combination with vinorelbine 30 mg/m2 D1,8 against breast cancer was studied. Of the 35 patients, 15 had previously received neoadjuvant treatment based on anthracyclines, 11 treatment with taxanes and 6 patients with both. The objective response rate was 53.1% and the median survival time was 22 months. Grade 3/4 neutropenia was observed in 44% of cycles, and febrile neutropenia was seen in 4 patients (11.4%). No grade 3/4 nephrotoxicity or neuropathy was noted. This combination was effective and well tolerated in patients with MBC. The authors proposed this scheme as first-line treatment.

In a Phase II study on the efficacy and toxicity of Lipoplatin in combination with 5-fluorodeoxyuridine and radiation therapy against advanced gastric tumors 4 out of 5 patients (80%) receiving five weekly cycles of treatment achieved complete response and in a follow up of nine months (Koukourakis et al, 2009). The high response rate observed in this Phase II study is suggested to arise from the high vascularization of gastric tumors compared to other solid tumors thus resulting in high Lipoplatin concentration (similar data were also observed in the patient tumor targeting study) and from rupture of the nanoparticles by the process of radiation therapy (see Mechanism of Action). Thus, radiation therapy might be proven the most efficacious combination for Lipoplatin.

A registrational Phase II/III study against pancreatic cancer is in progress under the orphan drug status granted to Lipoplatin by the European Medicines Agency. The Company has received scientific advice by EMEA for a pivotal randomized Phase III study using Lipoplatin 200 mg/m2 D1,8 in combination with pemetrexed as first line in non-squamous NSCLC compared to cisplatin with pemetrexed.

Lipoplatin has successfully completed a Phase III trial for non-small cell lung cancer (NSCLC) Stathopoulos et al, 2010

Nephrotoxicity in arm A patients treated with lipoplatin–paclitaxel was 6.1%, while for arm B patients treated with cisplatin–paclitaxel, it was 40.0%, P value < 0.001. Some arm A patients had increased blood urea and serum creatinine but this was temporary and these patients eventually received the full nine cycles. Other side-effects with a statistically significant difference occurred in arm B where GI tract nausea, vomiting and fatigue were worse than in arm A. Myelotoxicity was higher in arm B patients and the difference was statistically significant for grade 3–4 neutropenia. Six patients in arm A and 10 in arm B were hospitalized due to febrile neutropenia. Anemia was common: 43.9% in arm A and 54.9% in arm B. Grades 1–4 leucopenia were 33.3% and 45.2% in arm A and B patients, respectively; grades 3 and 4 leucopenia were 12.3% and 2.6%, respectively, in arm A and 18.3% and 8.7%, respectively, in arm B (Table 2; statistically significant difference P value 0.017). Asthenia was more common in arm B patients (71.3% versus 57% in arm A, P value 0.019). The side- effect comparison was carried out for 229 patients in total. Stathopoulos et al, 2010

In a publication in Cancer Chemother Pharmacol, (Stathopoulos et al, 2011), exciting data were announced from a randomized Phase III study on Lipoplatin™ in the treatment of non-squamous non-small cell lung cancer (NSCLC). This study used Lipoplatin in combination with paclitaxel as first line treatment against non-squamous NSCLC and compared response rates and toxicities to a similar group of patients treated with cisplatin plus paclitaxel. This study has demonstrated statistically significant (p value = 0.036) increase in tumor response rate in the Lipoplatin arm (59.22% of patients) versus the cisplatin arm (42.42%, of patients) while also reducing most major toxicities of cisplatin, especially nephrotoxicity.

Attempts to develop platinum compounds to reduce the side effects of cisplatin have resulted in the introduction of carboplatin and oxaliplatin. However, both of these drugs have proven to have inferior response rates to cisplatin especially in lung cancer. Other cytotoxic agents such as taxanes (paclitaxel, docetaxel), gemcitabine, vinorelbine, pemetrexed, and irinotecan have also been used as substitutes of cisplatin; however, none of these agents has demonstrated superior efficacy to cisplatin in lung cancer. This Lipoplatin study represents the first time a drug has improved on cisplatin’s response rate in non-squamous NSCLC.

Median survival times were 10 months for the Lipoplatin arm and 8 months for the cisplatin arm, with a p-value of 0.155. The median duration of response was 7 months for the Lipoplatin arm and 6 months for the cisplatin arm. Although not statistically significant, these results suggest the potential for superior overall survival (OS) for Lipoplatin compared to cisplatin, a hypothesis that will be tested in a larger trial. Furthermore, among the responders to Lipoplatin a subgroup of patients demonstrated a substantially higher overall survival than a comparable subgroup of cisplatin responders. After 10 months, 30% of patients in the Lipoplatin arm, as compared with just 16% of patients in the cisplatin arm, were without disease progression. By the end of the trial, there were 32 patients alive, 21 from the Lipoplatin arm (20.39%) and 11 from the cisplatin arm (11.11%). Thus, after 18 months, the number of surviving patients was approximately double for Lipoplatin versus cisplatin.

The clinical development of Lipoplatin in adenocarcinomas establishes this drug as the most active platinum drug with significantly lower side effects.

In conclusion, the clinical data support replacement of cisplatin by Lipoplatin. Lipoplatin has substantially reduced the renal toxicity, peripheral neuropathy, ototoxicity, myelotoxicity as well as nausea/vomiting and asthenia of cisplatin in Phase I, II and III clinical studies with enhanced or similar efficacy to cisplatin.

Management Team

Executive Members

Teni Boulikas, Ph.D.

President, CEO

Founder of Regulon, the inventor of Lipoplatin and CEO. Teni holds a B.Sc. degree in Chemistry from the Aristotelian University of Thessaloniki and a Ph.D. from the Southwestern Medical School in Dallas, Texas in Biochemistry.

As a EMBO postdoctoral fellow, Teni studied at the Swiss Institute for Experimental Cancer Research in Epalinges sur Lausanne. He became Assistant Professor of Biochemistry, Head of the Laboratory of Monoclonal Antibodies at the University of Sherbrooke in Quebec. Teni then moved to the Linus Pauling Institute in Palo Alto as an Investigator and Director of the Laboratory of Molecular Carcinogenesis and later at the Institute of Molecular Medical Sciences (Palo Alto). In 1998 he founded Regulon based on a patent for the isolation of Regulatory DNA sequences (thus the name of the Company) and their cloning to express poisonous genes in specific cancers. He is also the inventor of liposomal encapsulation of cisplatin and many other drugs. He has over 80 publications. Teni’s passion is to invent new formulations to improve human health.

Tel: +30 6937 255 067
Email: teni@regulon.com

Theodoros Sazaklis MBA

CFO

Joined Regulon, Inc., in 2016 as Chief Financial Officer. Before that he had a long career in Banking and Asset Management. He was a Senior Director at Eurobank Asset Management, Head of Credit and ABS Trading at Eurobank, Deputy Director of Fixed Income and Structured Products at Emporiki Investment Bank, Deputy Investment Manager and Head of Fixed Income at Intertrust Mutual Funds and Interamerican Insurance and Senior Interest Rate Dealer at Intesa SanPaolo Bank. In addition, he was a consultant to Regulon Inc. since 2011. He holds an MBA from Imperial College. He holds a BSc in Computer Science from University of Athens with Honors (highest GPA score since Department’s inception) and a BA in Economics from University of Athens.

Email: theo@regulon.com

Celik Hatipoglu

Senior Vice President, Business Development and Sales

He graduated from the Department of Chemical Engineering of Hacettepe University in Ankara, Turkey. He has worked in the pharmaceutical sector in Turkey as executive manager in various departments like Business Development, Marketing and Sales for nearly 15 years. Çelik has been a member of the Regulon team since 2015 as General Manager of Regulon Turkey and has been serving as Vice President of Business Development and Sales since September 2017.

Email: celik.hatipoglu@regulon.com

Stavros Kottaridis, Ph.D.

Member of the BOD, Coordinator of Phase III in Greece

He has represented Greece in all major virus strikes at a European level. He is also a member of the EOF (Greek FDA) committee on biological drugs. As a director of the Papanikolaou Research Center at Agios Savvas Anticancer Hospital in Athens for 25 years he collaborated with almost every oncologist in the country providing expertise assistance with tissue culture and a plethora of other oncology studies. This role of Stavros was decisive in recruiting oncology centers in the Phase III studies of Lipoplatin in Greece and supervising the clinical development of the drug.

Email: stavros.kottaridis@regulon.com

Ted Doukas

Senior VP, Business USA

Ted is responsible for the Corporate office of Regulon in Melville, New York. A flourishing financier and real estate developer in the U.S. and abroad, Ted Doukas began his investment career in Long Island NY, where acquiring first class office, retail and residential properties throughout affluent Nassau and Suffolk Counties, he became one of the largest individual property in the area’s history. As volatility in the real estate market spread, Doukas’ abilities to develop and turnaround complex projects has led him to extensively expand his work into the beleaguered markets. Born in Greece, Doukas studied Medicine for two years at the University of Pisa in Italy before coming to the U.S. where he was educated in Business at New York Institute of Technology. Ted is recognized throughout a myriad of industries for his creative thinking and ability to profitably implement critical growth-oriented policies.

Email: ted.doukas@regulon.com

Christina Karipi M.D

Member of Board of Directors

Christine joined Regulon, Inc (USA) as a Member of Board of Directors in 2009 and Regulon AE (Greece) as a Medical Officer in 2007. Dr. Karipi has been responsible for the introduction of Lipoplatin™ at the Sotiria Pulmonary Disease Hospital in a Phase III study as first line against non-small cell lung cancer. She holds her Medical degree from the Medical School of Athens, Greece and her specialization at the 4th Clinic of the Sotiria Pulmonary Disease Hospital. She has represented Regulon in several business meetings.

Email: c.karipi@regulon.com

Andrei Lyne

Senior VP, Business Development

He holds a BA from Oxford University (Baker Scholarship), his MBA from NY University (Director's Fellowship). Andrei has over 10 years of experience focused on the life sciences sector. Prior to joining Regulon in 2009 he was an Executive Director in UBS Investment Bank's Global Healthcare Group, providing corporate development and financial advice to life science companies globally. At UBS, Andrei was instrumental in several dozen key client transactions, including six IPOs across the US and Europe that raised over $1.3 billion for pharmaceutical, biotech and other life science companies. He also completed over $3 billion of other equity, equity-linked and debt financing transactions and advised on many transformational M&A deals.

Tel: +1-917-484-1315 Email: andreilyne@gmail.com

Constantinos M. Paleos, Ph.D.

Scientific Director

Born in Chios, Greece, and obtained his BS in Chemistry from Athens University and his PhD from Drexel University in Philadelphia. In 1973, after three years with Amoco Chemicals and Motor Oil (Hellas), he joined the Institute of Physical Chemistry at NCSR “Demokritos”, where he was elected Director for the periods 1994-1999 and 2001-2007 while currently he is collaborating with this Institute. He was elected, in the periods 1994-1996 and 2005-2006 Vice President of Board of NCSR Demokritos. From 2002 he is consultant at Regulon, Inc. In 1991-1992 he was elected visiting professor at Louis Pasteur University, Strasbourg. His research activities focus in the area of “Nanomaterials of Supramolecular Organized Structure” including the synthesis and characterization of liquid crystals, molecular recognition of liposomal aggregates, modeling cell processes, preparation and characterization of multifunctional dendritic polymers, liposomes, drug and gene delivery systems and molecular transporters. He has published 178 original articles and reviews and his work has received over 3750 citations, (Source ISI, h-index 32).

Email: c.paleos@inn.demokritos.gr

Maria Stergoudi (Mirella), M.D.

Chief Medical Officer

has graduated from the Medical School of the Kapodistrian University of Athens, Greece. Following a graduate program, she has worked with physicians of different expertize in central hospitals of Athens. She joined Regulon in 2010 as a Medical Officer, working intensively coordinating clinical studies, communicating with oncologists and initiating sites worldwide, preparing all necessary study reference documents (protocols, ICFs, CRFs), as well as reports for local Regulatory Authorities. Mirella acts as the link between Regulon and physicians, being always on alert to clarify issues regarding criteria of eligibility, treatment regimens, dose schemes and modifications and handling possible AEs. She has represented Regulon at the meetings with EMA and MHRA team in 2012, where dossiers for both Lipoplatin and Nanoplatin were successfully presented.

Email: mirella.stergoudi@regulon.com

Alexandros Pantos, Ph.D.

Chemistry, R&D, Production

Alex has graduated from the Chemistry Department of the Kapodistrian University of Athens, Greece and received his M.Sc and Ph.D in Drug Delivery. During his post-graduated studies he obtained EPEAEK Fellowship for MSc Studies from Athens University and Fellowship for Excellency Research - GSRT, Greece. He is an expert in preparation and characterization of drug loaded multifunctional liposomes and modified dendrimers /hyperbranched polymers for prospected applications as drug delivery systems. Alex is specialized in several nanoparticle characterization techniques including thermal analysis (ITC, microDSC). His fields of current interests also include: studies on the mechanism of adhesion and fusion of multifunctional liposomal systems resulting in formation of multicompartment systems which are model of cell interactions. He is author of many presentations and scientific publications in several high impact journals in the field of Nanotechnology such as: Langmuir, ChemMedChem, BBA, Accounts in Chemical Research. He joined Regulon in 2005 as a Senior Project Chemist and since 2010 is responsible for the Quality Control of Regulon’s products.

Email: alexandros@regulon.com

Nikolaos Boulikas

Information Technology & Software Engineering

Nikolaos is an expert in Information Technology. He has a critical mind in presenting our technology and he masters electronic data management including data on clinical studies and presentation of documents. He has hard-coded our proprietary production software needed to run automation and also possesses web designing skills. His recent achievement is the setting of a web program for electronic data capture on patients enrolled in Lipoplatin’s pivotal clinical trials.

Email: niko@boulikas.com

Butenko Alexander Borisovich, Ph.D

Deputy General Director of Regulon in Russia

Assistant Professor, Head physician of the rehabilitation center in Moscow, Deputy General Director of Regulon in Russia. A. Butenko has published 84 scientific works and 2 inventions in the field of clinical biochemistry and oncology. A. Butenko took part directly in the development of the efficacious treatment schemes for solid malignant tumor by using Lipoplatin in collaboration with the team of Regulon in Athens. A. Butenko has extensive clinical experience in the treatment of terminally ill cancer patients who were refused treatment in hospitals because of the advanced stage of their disease. Such patients include those with stomach, colon, pancreas, nervous system and lung cancers.

Email: alexander.butenko@regulon.com

Deniz Yüce, MD, Ph.D

Oncologist Regulon Turekey; Department of Preventive Oncology of Hacettepe University Cancer Institute

Deniz is a Specialist in Preventive Oncology and Instructor at Department of Preventive Oncology of Hacettepe University Cancer Institute. Deniz received his Medical degree from Gazi University Faculty of Medicine in 2005 and his MSc in Cancer Epidemiology from Hacettepe University Cancer Institute, Department of Preventive Oncology in 2011. He then obtained his PhD from the Department of Epidemiology, Hacettepe University Public Health Institute in 2012. He worked as Physician in Turkish Red Crescent, Ankara, TURKEY in 2005, as a Physician at the Emergency Department in Akay Private Hospital, Ankara, TURKEY in 2008, as Research Assistant in Hacettepe University in 2009, as a Specialist in Preventive Oncology in 2012 and as Medical Advisor in Regulon Inc. Turkey since 2014. He is responsible for the treatment of cancer patients in Turkey in a number of different cancers with Lipoplatin, including breast, lung, ovarian, and others.

Email: deniz.yuce@regulon.com

Publications

Clinical Publications

A Phase II Study of Lipoplatin (Liposomal Cisplatin)/Vinorelbine Combination in HER-2/ neu–Negative Metastatic Breast Cancer
Fadi S. Farhat, MD • 1 Sally Temraz, MD • 2 Joseph Kattan, MD • 3 Khaled Ibrahim, MD • 1 Nizar Bitar, MD • 4 • 5 Nadine Haddad • 6 Rahif Jalloul, MD • 5 Hassan A. Hatoum, MD • 2 Ghazi Nsouli, MD • 5 Ali I. Shamseddine, MD2

Comparison of liposomal cisplatin versus cisplatin in non-squamous cell non-small-cell lung cancer
G. P. Stathopoulos • D. Antoniou • J. Dimitroulis • J. Stathopoulos • K. Marosis • P. Michalopoulou


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